Ten patients with chronic hepatitis type D were treated during 4 months with alpha lymphoblastoid interferon in combination with two 2-week courses of acyclovir. Median percentage of HDAg-positive hepatocytes decreased from 11 to 1, p = 0.0225. Patients with no liver HDAg expression after treatment (n = 5) showed improved AST levels (normal in 4) and diminished liver cell inflammation. One patient, who cleared HDAg has complete biochemical remission of his liver disease with 2 years of follow-up. Five patients with persistent, albeit low, HDAg expression in the liver, had continued liver cell destruction (AST elevated and/or abnormal biopsy). No evidence for an enhancing effect of acyclovir for interferon therapy was observed.