In 1952, a semester before Ernesto "Fuser" Guevara is due to complete his medical degree, he and his older friend Alberto Granado, a biochemist, leave Buenos Aires to travel across South America. While there is a goal at the end of their journey - they intend to work in a leper colony in Peru - the main purpose is initially fun and adventure. They desire to see as much of Latin America as they can, more than in just four and a half months, while Granado's purpose is also to bed as many women as will fall for his pickup lines. Their initial method of transport is Granado's dilapidated Norton 500 motorcycle christened "La Poderosa" ("The Mighty One").