The story of the conflict between slave-traders and Jesuits during the colonisation of South America by Spain and Portugal. In 1750 Jesuit priest Gabriel (Jeremy Irons) arrives in the Amazon to build a mission for the Guarani Indians. He comes into conflict with slave trader Mendoza (Robert De Niro), who kills or captures many of the tribe but escapes punishment due to the fact that he is an aristocrat. However, it transpires that even Mendoza has a conscience when he comes to Gabriel asking for penance.