We detected a severe defect in concanavalin A-induced suppressor-cell activity in 22 patients with "autoimmune" chronic active hepatitis and in 26 patients with hepatitis B surface antigen (HBsAg)-positive chronic active hepatitis, as compared with 20 control subjects (P less than 0.01). Normal values were observed in 21 patients with "autoimmune" hepatitis in whom a remission had been induced and maintained by treatment with prednisolone. When lymphocytes from patients with autoimmune chronic active hepatitis were preincubated with low-dose prednisolone in vitro, suppressor-cell activity was substantially improved (P less than 0.01), but no clear effect of prednisolone was seen in cells from patients with HBsAg-positive chronic active hepatitis. The loss of suppressor-cell activity in chronic active hepatitis may allow liver damage to continue, and the reversal of the defect in the autoimmune form of the disease by administration of low-dose prednisolone provides a plausible explanation for the efficacy of this treatment. The contrasting in vitro responses to prednisolone in autoimmune and HBsAg-positive chronic active hepatitis suggest that the fundamental nature of the suppressor-cell defect may be different in these two forms of the disease.