Clinical resistance to primary, secondary, and tertiary infections with Leishmania tropica, cellular- and humoral-immune responses, and the effects of antilymphocyte globulin (ALG) therapy on these parameters were studied in rhesus monkeys. Cellular immunity was assessed by in vitro blastoid transformation of lymphocytes in the presence of L. tropica antigen. Humoral-immune response was detected by the agglutination of trypsinized organisms. In the monkeys, it was found that (a) immunity did not follow cutaneous infection with L. tropica as it usually does in man, (b) in vitro transformation of peripheral blood lymphocytes and the production of agglutinating antibody was delayed by ALG therapy before infection, (c) altered in vitro lymphocyte responses with normal antibody response were observed in animals injected with ALG before reinfection, after primary infection without such manipulation, and (d) there was no evidence of metastasis or visceralization. These results suggest that immunity to L. tropica in monkeys is in some ways qualitatively and quantitatively different from that in humans and that multiple host-immune factors are operative in resistance to this parasite.