Cerulean Cave was slightly redesigned for the U.S. release of Red and Blue for concern that the dungeon would be too difficult for American players.
Koffing and Weezing's original prototype names were NY and LA referring to the polluted cities of New York and Los Angeles.
Satoshi Tajiri wanted to have the Pokémon faint instead of die for two reasons, one was to not make the game excessively violent and to not have children equate death with losing.
Mew was not going to be included in the game but was then added after the debug features were removed to fill in the empty space.
Initially there was going to be more than 150 Pokemon but several were removed from the final product.