Autologous mixed lymphocyte reaction (AMLR) and T cell subsets defined with monoclonal antibodies were analyzed in the peripheral blood of homosexual males with Kaposi's sarcoma (KS). All seven patients demonstrated decreased AMLR (P less than 0.001) when compared with age- and sex-matched simultaneously studied controls. These patients also showed decreased proportions of Leu-3+ (helper/inducer phenotype) and an increase in the proportion of Leu-2+ (suppressor/cytotoxic phenotype) T cells. Leu-3+ T cells were purified from two patients by depleting Leu-2+ T cells in complement-dependent cytotoxicity. Leu-3+ T cells from both patients demonstrated poor proliferative response in the AMLR. In allogeneic MLR, patients' T cells were poor responders and their non-T cells were poor stimulators against healthy controls. This study demonstrates deficiency of both AMLR and allogeneic MLR in patients with KS. The decreased AMLR is associated with qualitative and functional deficiency of Leu-3+ responder T cells. Whether the functional deficiency of Leu-3+ responder T cells in the AMLR is a general phenomena or a feature of a subset of patients with KS remains to be determined.