The effect of a commercially available intravenous gammaglobulin preparation (IgSRK; Sandoglobulin) on the antigen-non-specific activation of the immune system was examined using pokeweed mitogen (PWM)-induced B cell differentiation. In cultures of peripheral blood mononuclear cells from 16 normal donors, IgSRK (300 micrograms/ml) inhibited PWM-induced generation of plaque-forming cells by 76% (P less than 0.001), whereas human serum albumin (300 micrograms/ml) induced no significant inhibition (5%; P not significant). The IgSRK-mediated suppression was demonstrable in both serum-containing (76%) and serum-free (63%) media, and monomeric IgSRK suppressed as effectively as did heat-aggregated IgSRK. F(ab')2 fragments exhibited no inhibitory capacity (mean inhibition -11%; P not significant) suggesting that the Fc portion of IgSRK may be required for suppression. In addition, IgSRK had to be added to the cultures at their initiation to effect full inhibition. These studies suggest a potential beneficial pharmacological role for IgSRK in the treatment of disorders characterized by pathogenic autoantibodies, but also warn of a potential deleterious effect of inhibiting the host's humoral response to an infectious challenge.