At the beginning of the games, the player can choose Bulbasaur, Charmander or Squirtle as their starter Pokémon from Professor Oak. After that choice, they cannot catch the other two starters or their evolutions in the wild or by trading with in-game NPCs, so, to complete the Pokédex, the player must link games and trade with other players in the real world. The basic story is to become the best trainer in all of Kanto; this is done by raising Pokémon, defeating Gym Leaders for Badges, and eventually challenging the Elite Four, the greatest Trainers in the land.

The player has a childhood rival, the grandson of Professor Oak. This character's default name is the color of the version owned (i.e. in Red version, the character's default name is Red). If one plays Red, the rival is Blue. He will repeatedly battle the player at certain points in the game to test the player's Pokémon; being defeated is an indication for the player to level up his or her team. He will always choose for his starter a Pokémon that has a type advantage over the player's chosen one; for example, if the player chooses Squirtle, he will choose Bulbasaur, a Grass-type Pokémon, giving it an advantage over Water-type Squirtle.

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