The present study was undertaken to determine the nature of the immunoregulatory T-cell defect after autologous mixed lymphocyte reaction (AMLR) activation in patients with systemic lupus erythematosus (SLE). Although AMLR was decreased in patients with SLE compared with normals, there was no difference in major proliferative cells (T4 cells and T4+JRA+ subset) in response to AMLR. Functional activity of AMLR-stimulated T4 subsets in patients with SLE and normals was examined in helper and suppressor/inducer assay, using pokeweed mitogen (PWM)-driven IgG synthesis. The T4+JRA- (helper) subset from SLE patients showed no greater activity than normals. However the T4+JRA+ (suppressor/inducer) subset from SLE patients showed decreased suppression induction compared with normals. This defect in the suppressor/inducer function was demonstrated even in patients with inactive SLR or in remission.