Suppressor cell function was studied in twenty-nine patients with chronic active hepatitis (CAH) in relation to possible aetiological causes and activity of liver disease. All fifteen patients with evidence of viral aetiology (ten HBsAg-positive CAH and five non-A, non-B CAH) showed normal suppressor cell function independently of severity of liver damage. In contrast, fourteen patients with HBsAg-negative CAH, including four cases with circulating antibodies to the hepatitis B virus, demonstrated a significant reduction in supprpessor cell activity compared to control subjects. No significant difference was found in this group between cases with and without circulating autoantibodies. In four out of five HBsAg-negative patients tested serially suppressor cell defect correlated with disease activity suggesting an abnormality in the regulation rather than a depletion of suppressor cells. These results suggest that different mechanisms are responsible for autoimmunity to the liver in virus and non-virus-related CAH.