A low dosage of human leukocyte interferon was intramuscularly given to 47 patients with hepatitis B surface antigen (HBsAg) positive chronic active hepatitis once a week for 4 consecutive weeks (10 X 10(5), 5 X 10(5), 2 X 10(5) and 1 X 10(5) U). After treatment, a reduction of serum HBsAg was observed in 26 patients; 3 of them showed no serum HBsAg and 1 of the 3 appeared to produce antibody to HBsAg. 31 of 34 patients investigated showed a significant decrease in Dane particle-associated DNA-polymerase activity (p less than 0.001). Among 17 patients positive for hepatitis B e antigen (HBeAg), 10 of them seroconverted to anti-HBe. Serum transaminase levels also significantly improved in 34 of 38 patients (p less than 0.001). Our findings indicate that a low dosage of human leukocyte interferon such as 18 X 10(5) U, administered in progressively decreasing doses, may be effective in the treatment of chronic hepatitis B virus infection.