A total of 54 patients hospitalized for chronic active hepatitis were randomly treated, 29 with prednisolone (maintenance dose 15 mg/day) and 25 with depot synthetic corticotrophin (maintenance dose 1 mg/week, i.m.) and were followed up for 6 to 24 months or longer. In this series, young males predominated, the incidence of serum HBsAg positivity approached 80% in both treatment and no patient had initial evidence of cirrhosis or had autoimmune associated diseases. With either drug SGOT levels showed a decrease during the initial 12 months of therapy (p less than 0.05); initial jaundice, when present, had disappeared by the 3rd month of treatment. With both treatments globulins and gamma-globulins decreased significantly after 12 to 24 months of therapy. Serum HBsAg persisted in all but two cases. Serum liver biopsies showed the following evolutions of histological activity: 12 cases (22%) improved to the "inactive phase" (8 with prednisolone and 4 with corticotrophin); 19 (35%) improved to a lesser extent (8 with prednisolone and 11 with corticotrophin); 17 (32%) remained unchanged (11 with prednisolone and 6 with corticotrophin); 6 (11%) worsened (2 with prednisolone and 4 with corticotrophin). Morphological features of cirrhosis appearently developed in 15 patients (8 treated with prednisolone and 7 with corticotrophin) of whom 7 achieved improvement of histological aggressiveness concurrently. Differences between treatments were not significant. Side effects suggesting drug discontinuation occurred only in 6 cases.