Sixty-six patients with hepatocellular carcinoma (HCC) in various stages of hepatic involvement were studied prospectively. Of these, 50 (75%) had associated cirrhosis and 19 (28%) had serum hepatitis B surface antigen (HBsAg). Six (9%) patients were eligible for tumor resection, 34 were selected for doxorubicin chemotherapy (60 mg/m2, i.v., given every 3 weeks, up to a maximum dose of 550 mg/m2), and 26 were followed up without treatment. Untreated patients survived 1-18 months (median 1) after diagnosis. Surgically treated patients survived 1-14 months (median 4.5). In the doxorubicin group, six patients died soon after the first course of treatment, leaving 28 patients to be evaluated. Seven (24.5%) responded to therapy, surviving 2-26 months (median 8.0). Twenty-one (75.5%) did not respond to chemotherapy and had a median survival of 3.5 months (range: 2-12). Initial performance status and the degree of hepatic impairment were found to be covariates of prognostic significance. The type and severity of drug-related side-effects appeared to be comparable to those reported by others. In accordance with previous reports, our patients with HCC often had non-resectable tumors or responded poorly to chemotherapy. The association between this tumor and cirrhosis might partially account for treatment failure.