In patients with cutaneous leishmaniasis in areas of Leishmania braziliensis transmission, ulcers may heal without therapy. In the present study, we evaluated the T cell responses of 10 subjects who two years earlier had a rapidly (less than three months) self-healing cutaneous disease. The immunologic responses of these cases were determined by intradermal skin test, measurements of antibodies, lymphocyte proliferative responses, and interferon-gamma (IFN-gamma) production in cultures stimulated with Leishmania antigens. These data were compared with those observed in 10 other patients with active cutaneous and mucosal leishmaniasis. Evidence of strong lymphocyte blastogenesis and IFN-gamma production was observed in eight of 10 patients with self-healing cutaneous leishmaniasis, with stimulation indices ranging from 32 to 506, and IFN-gamma levels ranging from 500 to 2,900 pg/ml. The mean +/- SD stimulation index of the lymphocyte proliferative responses (288 +/- 247) and the mean +/- SD of IFN-gamma production after stimulation with Leishmania antigen (970 +/- 960 pg/ml) in subjects with self-healing cutaneous leishmaniasis were similar (P > 0.05) to those observed in patients with mucosal disease (stimulation index = 308 +/- 282 and IFN-gamma level = 838 +/- 819 pg/ml). These responses were higher (P < 0.01) than those observed in patients with active cutaneous leishmaniasis (stimulation index = 50 +/- 82 and IFN-gamma level = 264 +/- 336 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)