Eight patients with chronic hepatitis B entered a pilot study of gamma interferon and alpha interferon in combination. Gamma interferon alone had minimal inhibitory effects on serum levels of hepatitis B virus as monitored by serum HBV DNA and DNA-polymerase activity. The drug also gave troublesome side effects. In contrast, alpha interferon had more potent inhibitory effects on serum HBV levels and fewer side effects. When combined, the two interferons showed no additive or synergistic effects in inhibiting serum levels of HBV DNA or DNA polymerase. These findings indicate that the addition of gamma interferon to alpha interferon provides no additional antiviral effects but contributes significantly to side effects.