Pokeweed mitogen (PWM)-induced immunoglobulin (Ig) synthesis by peripheral blood mononuclear cells (PBL) from 33 patients with systemic lupus erythematosus (SLE) was compared to that synthesized by PBL from 22 normal individuals. Short-term unstimulated culture of SLE-PBL immediately after separation from PB revealed Ig synthesis 4 times that of normal PBL. However, SLE-PBL had a depressed PWM-induced Ig synthetic response that was partially, but not totally, related to active disease and was not correctable by co-culture with normal lymphocyte populations. In both the short-term-unstimulated and the PWM-stimulated cultures, IgM was the major Ig class synthesized by normal PBL, while IgM synthesis by SLE-PBL was depressed more than the other Ig classes. These results can best be explained by a preactivated PBL population in SLE.