Studies were undertaken to determine whether Trypanosoma cruzi can invade and multiply within human monocytes and macrophages cultured in vitro and, if so, whether macrophages can be activated to inhibit the multiplication. A reticulotropic strain of T. cruzi was capable of infecting human monocytes and monocyte-derived macrophages. Intracellular multiplication was observed in both cell types when they were examined microscopically. An increase in the number of trypanosomes occurred in the supernatants as well, providing additional evidence of intracellular multiplication and cell disruption by the parasite. Activation of monocyte-derived macrophages was accomplished by incubating the monolayers in the presence of lymphocytes and streptokinase-streptodornase. These activated macrophages inhibited intracellular multiplication of T. cruzi and the number of T. cruzi in the supernatants of these monolayers was markedly decreased as well.