Diminished lymphocyte proliferative responses to several mitogens have been demonstrated in peripheral blood lymphocytes (PBL) from patients with common variable hypogammaglobulinemia. The mechanism is obscure, although intrinsic cellular defects have been suggested in both T and B cells. We studied PBL from three patients with this disease, who showed diminished lymphocyte proliferative responses to pokeweed mitogen and/or concanavalin A. Decreased OKT4-reactive helper T-cell subsets as well as increased OKT8-reactive suppressor T-cell subsets, as defined by recently developed monoclonal antibodies, were identified in PBL from these patients. In addition, activated suppressor T-cell function modulating the proliferative responses of autologous and/or allogeneic lymphocytes was demonstrated in these patients by coculture of the patients' PBL with allogeneic PBL and by elimination of T-cell subsets from the patients' PBL.