Pharmacokinetics, tolerance and biological effects of human recombinant γ-interferon were studied in 12 patients with chronic active hepatitis B. Serum concentrations of γ-interferon were measured by radioimmunoassay in four patients after a subcutaneous injection of 10 million U (0.5 mg); the peak serum concentration of γ-interferon (29 ± 7 U/ml) was reached after 5 to 8 hr and γ-interferon remained detectable for 24 to 36 hr. Twelve patients received recombinant γ-interferon, 2.5 to 10 million U daily, for 4 mo. All suffered from a dose-dependent, flulike syndrome similar to that induced by α-interferon. Recombinant γ-interferon induced a marked increase of serum ALT and a significant decrease of serum hepatitis B virus-DNA. Serum hepatitis B virus-DNA disappeared in one patient during administration of recombinant γ-interferon. Serum hepatitis B virus-DNA disappeared in four additional patients, and HBeAg disappeared in two patients during the 12 mo after administration of recombinant γ-interferon. These results indicate that subcutaneous injection is suitable for administration of recombinant γ-interferon and that recombinant γ-interferon has an antiviral effect in patients with chronic active hepatitis B. (HEPATOLOGY 1990;12:155–158).