A prospective study was conducted to assess the safety and efficacy of the addition of oral verapamil to intravenous Adriamycin (doxorubicin) for the management of patients with unresectable hepatocellular carcinoma (HCC). All 28 patients studied had histologically verified disease, and cirrhosis was present in 20 of the 21 patients with adequate tissue sampling. The overall median survival was 57 days. Chemotherapy was terminated in seven patients after one course of treatment. Partial response and complete response were noted in four patients (19%) and one patient (4.8%), respectively, among the 21 patients evaluated. Side effects related to the chemotherapy were present in all patients studied. Death from fulminating sepsis occurred in three of the 13 patients with leukopenia. Symptomatic myocardial dysfunction developed in one patient. The addition of verapamil apparently did not potentiate the tumoricidal effect of systemic Adriamycin on HCC but probably did increase its complications.