Monoclonal antibodies recognizing different human T lymphocyte subpopulations were used to characterize peripheral blood T lymphocytes in patients with leprosy. An increase in the suppressor T lymphocyte subpopulation was seen only in lepromatous leprosy (BL-LL) patients. In contrast, patients who had erythema nodosum leprosum (ENL) showed a disturbance in immunoregulation seen as a decrease of the suppressor cell percentage and manifested by an increase in in vitro lymphoproliferative responses to both PPD and PHA. This imbalance was seen to normalize as patients improved clinically. There was no deviation from the normal values of the total T lymphocyte population. It is suggested, therefore, that ENL may be associated with an acute imbalance of T lymphocyte subpopulations. Since the suppressor T lymphocyte identified by the mononuclear antibody used is antigen nonspecific, the significance of these suppressor cells in the pathogenesis of leprosy remains unclear.