Chronic hepatitis B patients with active viral replication were treated with acyclovir, either orally 800 mg 4 times daily, or intravenously 15 mg/kg twice daily; duration of treatment was 4 weeks. A second course of intravenous acyclovir (15 mg/kg twice daily for 2 weeks) was given to 5 patients in combination with intramuscular lymphoblastoid alpha-interferon treatment (2.5 MU/m2, once daily). Oral acyclovir had no detectable effect on DNA-polymerase or HBeAg. Intravenous acyclovir alone depressed HBV replication and HBeAg, followed by prolonged negativity of DNA-polymerase in 4 out of 11 patients. Combination therapy of acyclovir with interferon had a significantly greater fall in DNA-polymerase and HBeAg than acyclovir alone. Apart from thrombophlebitis, therapy with acyclovir was tolerated well provided fluid intake was more than 2 litres daily. The combination therapy of acyclovir with interferon appears the most promising for conversion of a state of active viral replication into virus latency.