Abstract C57BL/6J mice were subjected to various combinations of immunosuppressive treatments and infected i.v. with amastigotes of Leishmania donovani. In normal mice the parasite population reached its peak about 24 days post-infection, after which parasite numbers gradually declined but they were still detectable on day 60. The course of infection was not altered in mice which had been thymectomized, lethally irradiated, and reconstituted with syngeneic marrow cells. Moderate lethally irradiated, and reconstituted with syngeneic marrow cells. Moderate suppression of acquired resistance resulted when thymectomized-irradiated mice were reconstituted with marrow cells which were previously treated with anti-brain associated θ serum and/or when recipient mice were treated with azathioprine on the same day they were infected. Splenectomy alone or together with irradiation failed to suppress immunity, but a long-lasting high level of immunosuppression resulted when splenectomy was combined with all the above treatments. These results suggest that 1) small numbers of thymus-dependent cells which survive irradiation and thymectomy or which may be present in the bone marrow may be sufficient to mount an immune response to L. donovani in mice, and 2) that T cells play an important role in acquired resistance to L. donovani in mice.