In coculture experiments with normal lymphocytes, peripheral blood lymphocytes (PBL) of 10 boys with hypogammaglobulinemia were screened for the presence of cells able to suppress Pokeweed mitogen (PWM)- and Staphylococcus aureus Cowan I-induced immunoglobulin production in vitro. PBL and T lymphocytes of two patients were shown to suppress reproducibly PWM-induced immunoglobulin production of control PBL and of control B + T lymphocytes. PBL of three other patients were also able to suppress but their activity was expressed only in combination with some but not other normal lymphocytes. In neither case was the Cowan I-induced response suppressed. PBL and T lymphocytes of one other patient were able to suppress both PWM- and S. aureus Cowan I-induced immunoglobulin production of normal lymphocytes. These data provide evidence for two functionally distinct suppressor T lymphocytes in hypogammaglobulinemic patients.