Opossums are considered natural predators of snakes and possess resistance to the venom of some viperids. The resistance of Didelphis to Crotalus venom has been demonstrated through biochemical and immunological assays. However, systematic observations on the behavior of adult Didelphis preying on venomous snakes have never been conducted. In this study the predatory and defensive behaviors of Didelphis marsupialis and Crotalus durissus, respectively, were analyzed in captivity. Defensive strategies showed by snakes included immobility, flight attempts, coiling, cocking, rattling, and counterattack with strikes and bites. The most common defensive behavior of the rattlesnakes was immobility. The way the opossums attacked was classified in three categories, depending on the defensive reactions presented by the snakes. On all occasions when the opossums were bitten, the injection of venom apparently did not affect the predation. The great ability in capturing and handling Crotalus durissus together with the apparent great tolerance to the venom shown by Didelphis marsupialis when preying on these snakes confirms the existent biochemical and immunological data about the resistance of opossums to crotalic venoms. In this way our data strongly reinforce the supposition that this species is an effective snake predator in nature.