A Phase II trial of combination therapy with recombinant leukocyte interferon (alpha IFN) and doxorubicin was performed in patients with unresectable hepatocellular carcinoma. alpha IFN was administered at a starting dose of 20 x 10(6) U/m2 intramuscularly or subcutaneously with doxorubicin 20 mg/m2 intravenously weekly x 3 weeks followed by a 2-week period rest. There were 22 patients entered into the study. Among the 21 patients, there were 2 partial responses (10%), one minor response, and one patient had stable disease. Toxicity was generally tolerable, with fever, fatigue, and myelosuppression being the most common side effects. This combination of weekly recombinant leukocytic interferon and doxorubicin has modest and limited activity in hepatocellular carcinoma.