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201 Spoiler warning: this article may contain major plot or ending details. 201
The plot follows the same storyline as Generation I, with the player beginning in Pallet Town. After meeting Professor Oak while trying to leave for Route 1, both the player and their rival are asked by Oak to choose a starter Pokémon, Bulbasaur, Charmander, or Squirtle, from the desk near him. Oak allows the player to choose first and the rival quickly gets jealous, chooses the starter whose type is supereffective against the player's starter, then challenges the player to a battle. During this Pokémon battle Professor Oak commentates.
After the battle, Oak allows the two new Trainers to leave for their journey across Kanto. Stopping in Viridian City's Poké Mart, the player will find that a package has come in for the professor, and the clerk asks that it be delivered to him. After this has been completed the professor gives one Pokédex to the player and one to the rival, and sends them on their way. Viridian City has a Gym; however, it is locked.
From here, the player has their first encounter with other Trainers, on Route 2 and in Viridian Forest, and their first encounter with a Gym Leader: Brock the Rock-type Gym Leader of Pewter City. After his defeat, journeying along Route 3 and through Mt. Moon brings the player face to face with the regional villainous team, Team Rocket, who are attempting to extract rare Fossils from the cave. Their defeat allows the player to continue through the cave, obtain the Dome Fossil or Helix Fossil which can be regenerated into Kabuto and Omanyte, and continue onto Route 4, which leads directly into Cerulean City, where another Gym is. This one, however, is run by Misty, and specializes in Water-type Pokémon. To the north, as well, there are two routes leading up to Bill's cottage. On the way, the player is confronted with a trainer who tries to persuade them to join Team Rocket. When the player reaches Bill's cottage and frees him of his transformation into a Clefairy, he will give the player a ticket for the S.S. Anne, a luxury ship moored in Vermilion Harbor and filled with Trainers. Taking a shortcut through a house burglarized by Team Rocket, the player finally arrives at Route 5.
After traveling down Routes 5 and 6, using the Underground Path to bypass Saffron City, the player finally arrives in Vermilion. This city is home to another Pokémon Gym; however, the way to it is blocked by a small tree. The only thing to do is to show the ticket to the Sailor guarding the harbor, allowing entry into the S.S. Anne. It is here, after assisting the captain with his seasickness, that the player will obtain the first of the seven Hidden Machines available in the game, containing Cut. With this, and the Cascade Badge, the tree blocking the way to Vermilion Gym can be easily cut through, and Lt. Surge, a Gym Leader specializing in Electric-types, can be challenged. From here, Route 11 beckons, as does Diglett's Cave, through which is the only way to get back to Route 2, and a second HM, containing Flash held by one of Professor Oak's aides on Route 2. The player takes a brief detour to Pewter City's museum's back entrance which was previously blocked due to a Cut-able tree, which can now easily be bypassed. The player obtains the Old Amber in the museum. Heading back to Diglett's Cave, and to Vermilion, the player must go to Cerulean and to the east, onto Route 9 and towards the Rock Tunnel.
Rock Tunnel, a still undeveloped natural tunnel between the sections of Route 10, is pitch black inside; for this reason, Flash is recommended, but not required, for navigation of it. Finally reaching Lavender Town, the only town in Kanto without a Pokémon Gym besides Pallet, there is not much to do; the local Pokémon Tower is haunted. From here, Route 8 leads to Saffron City, but it again must be bypassed by way of another Underground Path, which has its other entrance on Route 7, on the west side of Saffron. Celadon City, the home of the fourth Gym which specializes in Grass-type Pokémon, is just a short walk further. Like the Vermilion Gym, the Celadon Gym also has a small tree blocking the way to its entrance, and an old man outside.
The Rocket Game Corner in Celadon is not what it appears to be. In fact, the Game Corner itself is merely the above-ground portion of a sprawling underground complex: the Rocket Hideout. The Team Rocket boss, Giovanni, appears for the first time here, and after his defeat, flees, leaving behind a Silph Scope. A Silph Scope is required to fully navigate the Pokémon Tower inside of Lavender Town that the player encountered earlier.
After this, the Pokémon Tower can be navigated, and the ghosts haunting it are revealed to be Gastly and Haunter. In front of the stairs to the final floor, blocking the way, is also a final spirit, that of a deceased Marowak that was killed by Team Rocket when they captured her child. Making it all the way to the top reveals Mr. Fuji held hostage by Team Rocket grunts, who will leave when they are defeated. Fuji gives away the Poké Flute, and with that, the Snorlax blocking Route 11 and Route 16 can finally be moved away. Another HM, containing Fly, can be obtained easily by cutting away a tree blocking the northern section of Route 16.
Now the player is presented with a choice of how to get to Fuchsia City. Traveling down either way the Snorlax are blocking, a faster way via Routes 16, 17, and 18 on Cycling Road, or down the Silence Bridge of Routes 12, 13, 14, and 15, inevitably brings one to the southernmost city in continental Kanto, Fuchsia City, home of Koga of the Poisonous Fuchsia Gym and the Kanto Safari Zone. The Safari Zone is currently running a contest: the person to reach a specific rest house first will win yet another HM, containing Surf. Finding the Safari Zone Warden's Gold Teeth also will have him reward the player with the final of Kanto's HMs, containing Strength.
The player then goes back to either Celadon City or Lavender Town, encountering the other Snorlax on the way back. After stopping off at the Celadon Mansion and getting some Tea, Saffron City can finally be entered. However, Team Rocket is guarding almost every door in the city, including that of the local Pokémon Gym! One of the open buildings, however, is the unofficial Fighting-type Pokémon Gym. After the player defeats the Fighting Dojo, he/she is entitled to either a Hitmonchan or a Hitmonlee. The city's centerpiece building, Silph Co.'s headquarters, has also been infiltrated by the organization, and at the top, waiting in the boardroom, is the Team Rocket Boss, Giovanni, appearing for a second time, demanding that the president give him the Master Ball that the company had developed. After his defeat, he flees.
After Team Rocket clears out of Saffron City, all buildings previously blocked are now open, as well as the Gym. The Gym Leader, Sabrina, specializes in Psychic-types. The floor, as well, is covered in warp tiles that make it difficult to navigate. After Sabrina's defeat, the player makes his/her way back to Fuchsia City again and heads out to obtain the rest of the Badges.
With six Badges in hand, and five HMs in the TM Case, finally the player can adventure onto the open sea of Routes 19 and 20. A short way across them, of course, is a minor obstacle: the Seafoam Islands. After they have been navigated through, the player can continue on Route 20 to Cinnabar Island, home of Blaine's Fire-type Gym. There are also several more facilities on the island, including one that actually revives Pokémon Fossils. After Blaine's defeat, Bill shows up again, because he needs help in a small region south of Kanto, the Sevii Islands. If the player accepts, the Seagallop Ferry will travel to One Island, where a friend of Bill's, Celio, is attempting to connect the islands' PC system to that of Kanto. During this, there is also a crisis in Two Island, where the daughter of the owner of the Joyful Game Corner has gone missing, and in Three Island where a group of invading Bikers are causing trouble. After defeating them and finding the lost girl, Lostelle, who is in Berry Forest, Bill and the player will return to Kanto, where the final Gym, that of Viridian City, lies.
Finally unlocked, the Gym, whose leader specializes in Ground-types, is revealed to be none other than the boss of Team Rocket himself, Giovanni! After his defeat, he vows to disband Team Rocket and disappears. Now with eight Badges, all that lies ahead is the Pokémon League at Indigo Plateau, conveniently at the end of Route 23.
The Elite Four await challengers, those who have proven themselves worthy by getting all eight Badges and making it through Victory Road will face them, in order. Lorelei, who trains Ice-type Pokémon is first, followed by Bruno, whose specialty is Fighting, Agatha, whose specialty is Ghost, and finally Lance, who specializes in Dragon-types. After defeating these four, the reigning Pokémon Champion challenges the player to a final battle, and the Champion is none other than the player's own rival! After his defeat, Oak arrives and tells the player that they won because they care better for their Pokémon, and the player's current party are added to the Hall of Fame.
After the credits roll, the player is back in Pallet Town. Professor Oak will have the player come to his lab to check on the Pokédex, if the player has obtained at least 60 Pokémon he will then upgrade it to the National Pokédex, in which he will then ask the player to go back to the Sevii Islands to encounter Pokémon that Professor Oak has never before seen.
There is some more work that Celio needs to do on his network machine, as he wishes to link to yet another region. The signal, however, is not strong enough, and he needs the Ruby and the Sapphire, two items found in the Sevii Islands, to strengthen it. The Ruby is found deep in a cave in Mt. Ember, which Team Rocket grunts have been seen fooling around with. The Sapphire lies at the deepest part of the Dotted Hole in Ruin Valley. The Ruby can be given to Celio without a hitch; however, the Sapphire, when found, is stolen by a Scientist named Gideon, who takes it back to Team Rocket's warehouse in the Five Isle Meadow. By infiltrating the warehouse and defeating the remaining Rocket Admins, they realize that Giovanni has disbanded Team Rocket. They do, however, vow to return one day, and bring Team Rocket back to its former glory. Gideon reluctantly gives back the Sapphire, and after this, trades are possible with the Hoenn-based Pokémon Ruby, Sapphire, and Emerald. The Elite Four can once again be challenged, and their Pokémon are 12 levels higher, with some of them possessing new Pokémon. In addition, Cerulean Cave is now open, and the powerful Mewtwo can be found there. Entei, Suicune, or Raikou will also begin roaming the Kanto region, depending on whether the player chose Bulbasaur, Charmander, or Squirtle, respectively, as their starter Pokémon.