It has been shown that Trypanosoma cruzi-infected mice develop a nonspecific resistance to challenge with an unrelated microorganism, namely, Listeria monocytogenes. This increased resistance to Listeria was observed on the 4th day of trypanosoma infection and persisted for at least 25 days. It was associated with an increased mononuclear phagocytic activity, as revealed by carbon clearance experiments. The possibility that macrophages of the infected host become activated by a process which appears to depend upon some form of specific interaction between the immune lymphoid cells and the infecting organisms, as has been demonstrated with other infectious agents, is discussed.