Concanavalin A (Con A)–activated suppressor cell activity was determined in multiple sclerosis (MS) patients who had been assigned to one of three subgroups, those with active disease, those recovering from a flare-up, and those with stable disease. The level of suppression induced by the Con A–activated suppressor cells on the mitogenic response of autologous peripheral blood lymphocytes was reduced in patients with active disease (3 ± 8%) compared with stable patients (30 ± 8%), patients recovering from a flare-up (62 ± 5%), and controls (40 ± 5%). As a measure of the actual amounts of suppressor factors released, the effect of supernatants from the Con A–activated cells on the proliferative activity of a dividing cell line (L cells) was determined concurrently. The inhibitory effect of supernatants from activated cells was reduced in active and stable MS patients (7 ± 3%) compared to controls (21 ± 4%). Three of 4 with active MS showed mildly elevated immune complex levels as measured by the Raji cell technique; each of these patients had low suppressor activity. Levamisole (1 μg per milliliter) failed to alter suppresor cell activity in our in vitro system.