Activated suppressor cell function, induced with either concanavalin A or OKT3 and mediated by either unfractionated mononuclear cells or "panning" enriched T8+ cells, freshly isolated from peripheral blood, is reduced in patients with progressive multiple sclerosis (MS) as compared with control donors. In this study, we generated T8+ cell lines from the peripheral blood of these same patients and controls. Suppressor activity, mediated by T8+ cells exposed to OKT3 on days 1, 7, and 14 of culture and then treated with mitomycin C on day 16, was significantly reduced in the MS group (mean percent suppression 13% +/- 5) as compared with the control group (68% +/- 6, n = 8, p less than 0.001). No differences were noted in [3H]thymidine uptake by the OKT3-stimulated T8+ cell lines of MS and control groups. Mean percent suppression mediated by T4+ cell lines did not differ between MS and control groups (15% +/- 4, n = 3, vs 22% +/- 2, n = 4). These current data suggest that the previously observed defect in T8+ cell-mediated activated suppressor cell function in MS is a persistent one, favoring the postulate that the defect reflects intrinsic alterations in this cell population rather than a transient effect of serum factors on T8+ cell function.