Fourteen out of 28 HBsAg/HBeAg-positive carriers with chronic persistent and active hepatitis were randomly assigned to human leukocyte interferon (a-IFN) treatment for three months. The remaining 14 patients served as controls. Each treated subject received a standard i.m. dose of 0.7-1.0 X 10(5)/kg/day reference units of a-IFN for 28 consecutive days, and then the same dose twice a week for two months. This treatment regimen was well tolerated, and no remarkable side effects were recorded. At six months the number of patients who permanently lost HBV-DNA from serum was significantly higher in the treated group (p = 0.006) than in the untreated group. These results suggest that a less expensive and well tolerated treatment regimen based on low dosage of a-IFN may be as effective in producing permanent inhibition of hepatitis B virus replication as a treatment regimen based on larger dosage.