Hepatitis due to hepatitis delta virus (HDV) infection is generally associated with severe histological abnormalities and rapid progression of the disease. To assess the efficacy of recombinant interferon‐a2b in treatment of chronic delta hepatitis, 22 patients were entered into a randomized controlled trial: 11 received interferon‐a2b subcutaneously three times weekly for 12 months (5 MU/m2for 4 months and then 3 MU/ m2for a further 8 months) and 11 were untreated. All patients were followed up for 6 months after the completion of therapy. Nine treated patients completed the trial: one was withdrawn with hyperthyroidism and one committed suicide. Serum ALT levels were normalized or significantly reduced, always within 3 months of initiating treatment, and remained so in 73% of treated patients at the 4th month and in 54.5% at the 12th month, compared with 18% and 18%, respectively, in the untreated group. Moreover, in seven of nine treated patients, interferon was associated with the clearance of serum HDV‐RNA, associated with amelioration of the histological picture, whereas this occurred in only four of 11 untreated patients. On cessation of therapy, all patients but one experienced a biological and/ or virological relapse over the 6‐month follow up. In conclusion, our data confirm that HDV is sensitive to inhibition by interferon‐a2b, although the schedule used did not achieve permanent control of the disease. The adverse effects of interferon require consideration; in particular, care will be needed to avoid serious psychiatric sid