Patients with progressive multiple sclerosis (MS) and controls were compared with regard to: (a) in vitro pokeweed mitogen (pwm)-induced IgG secretion, as an indirect measure of T8+ cell-mediated suppressor function; (b) alloantigen-directed cytotoxic activity, a predominantly T8+ cell-mediated function. The MS group had increased IgG secretion (4790 +/- 372 ng/ml vs. 1866 +/- 233 ng/ml, P less than 0.001) compared to controls. In contrast, alloantigen-directed cytotoxic activity did not differ between MS and control groups. These results suggest a selective defect of suppressor cell function in MS rather than a generalized dysfunction of T8+ cells. Defective immunoregulatory control coupled with preserved effector functions may contribute to the autoimmune process, suspected to underlie the pathogenesis of MS.