Cell-mediated immune (CMI) responses are important in the immunity against Leishmania spp. infection in man. However, an infection continues to persist for a limited or indefinite period of time in spite of demonstrable CMI. The factors which allow the infection to persist in the presence of the CMI are hitherto unknown. Evidence is presented here that Leishmania tropica or their products suppress the in vitro proliferative response of normal human lymphocytes to mitogen and specific antigens. The suppressive effect of L. tropica is neither due to a direct toxic action on lymphocytes nor to competition for nutrients or antigens. In vivo such an immunosuppressive effect could both facilitate macrophage parasitization and the intracellular survival of L. tropica, even after the CMI develops to processed L. tropica antigen. Persistence of infection is seen in many other bacterial, viral and fungal infections. The in vitro suppressive effect of L. tropica on the immune response observed in our study therefore becomes relevant to the understanding of the host-parasite interaction, which may determine the eventual outcome of infection in many other intracellular infections.