A pilot study has been designed in order to determine the tolerance and effectiveness of recombinant interferon gamma (rIFN-gamma) in chronic hepatitis B virus (HBV) infection. Eight HBsAg, HBeAg, HBV-DNAp and HBV-DNA-positive patients were randomly assigned to one of two groups. In group 1, 0.25 mg of rIFN-gamma/m2 body surface was administered daily for 28 days to 4 patients. In group 2, 0.10 mg of rIFN-gamma was administered to 4 patients under the same conditions. All the patients concluded the treatment and were observed over 11 more months. During treatment, 6 out of 8 patients showed decreased levels of HBV-DNA and HBV-DNAp. In addition, by the 8th month of follow-up, six patients became negative for HBV-DNAp and 2 for HBcAg; all patients remained positive for HBV-DNA. At the end of the study, only 2 patients remained negative for HBV-DNAp, 4 for HBcAg and one became negative for HBV-DNA. No differences in antiviral effect were observed between the two groups. Furthermore, the T4/T8 lymphocytes ratio increased during therapy. In conclusion, rIFN-gamma may play a role in the treatment of chronic HBV infection.