In this pilot study, 12 patients with chronic delta hepatitis were studied. The diagnosis was based on the presence of antibodies to the hepatitis delta antigen in the serum and hepatitis delta virus RNA and hepatitis delta antigen in the serum and liver. All patients were also positive for hepatitis B surface antigen. The infection was presumed to have been transmitted by intravenous drug abuse in six of the patients, blood transfusion in one and by sexual contact in four (two had antibodies to human immunodeficiency vims in their serum, but did not show signs of acquired immunodeficiency syndrome). In one further patient, the source of infection was unknown. Interferon alfa-2b (INTRON A, Schering-Plough Corporation) was initiated at S million units per day subcutaneously for at least 4 months, being reduced by half if side effects occurred. Serum alanine aminotransferase levels, hepatitis delta virus RNA and hepatitis delta antigen were measured at monthly intervals for up to 12 months in some patients. Interferon therapy resulted in decreased serum levels of these three markers. On cessation of therapy, most patients experienced a relapse over 6 months, but alanine aminotransferase levels could be normalized once more by restarting interferon therapy. In conclusion, interferon decreased hepatic inflammation by the inhibition of hepatitis delta virus replication, although relapse occurred when interferon was stopped and long-term therapy is required to achieve permanent control of the disease. Care will be required when treating patients with advanced or decompensated liver disease.