Eighty percent of 31 untreated patients with systemic lupus erythematosus (SLE) had abnormalities in their spontaneously expanded and/or Con-A-induced suppressor cell function, but the association of defects detected with both systems was only 68%. Loss of spontaneous suppression related positively to disease activity (r = 0.641) and the number of T gamma cells (r = 0.624) whereas Con-A-induced suppression correlated negatively with disease activity (r = -0.456) and the number of T gamma cells (r = 0.089). Incubation of mononuclear cells from SLE patients in antiribonucleoprotein IgG caused further loss of suppression in some, but not all, instances. The suppressor cell dysfunction found in SLE may result from diverse mechanisms, including a basic defect in the generation of suppressor cells and the abrogation of suppressor function by autoantibodies.