The effect of the supplementation with several gammaglobulin (GG) preparations on the in vitro immunoglobulin synthesis of peripheral blood mononuclear cells (PBMC) from normal subjects stimulated with pokeweed mitogen (PWM) was studied. Among the GG preparations used in this study, immune serum globulin (ISG) demonstrated the most suppressive effect, and S-sulfonation and polyethylene glycol (PEG)-treated preparations also had a suppressive effect. However, the preparation of pepsin degradation had no suppressive effect. And because IgG F(ab')2 fragments also failed to induce the suppressive effect, it was considered to be triggered by the attachment of the Fc portion of GG to the corresponding membrane receptor. To determine the cellular targets, PBMC were fractionated into E-rosetting cells (T cells) and non E-rosetting cells (B cells). The suppressive effect was induced by pre-incubation of either T cells or B cells with the GG preparations for 1 h, at 37 degrees C in PWM-induced immunoglobulin (Ig) production. The failure of T cells pretreated with OKT8 monoclonal antibody and complement to induce the suppressive effect suggested that T8 positive T cells are one of the effector cells involved. The activation step of the suppressive effect was prostaglandin E2-independent, and as effector cells contain an Fc receptor which is sensitive to pronase, it was suggested that monocytes were not involved in this activation process. Our observations further suggested that the Ig effects of GG therapy are not limited to antibody transfer, since GG preparations also suppress directly the differentiation of B cells and induce suppressor T cells in in vitro immunoglobulin production stimulated with PWM.