We investigated the long-term outcome of percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC). A series of 184 HCC patients received PEI as the sole anticancer treatment over an 8-year period, December, 1987, to December, 1995. Ninety-four patients had a single tumor < or = 3 cm, 50 patients had a single lesion of 3.1-5 cm, and 40 patients had multiple nodules (up to four) < or = 3 cm each. All patients had liver cirrhosis, classified as Child-Pugh class A in 127 cases and as Child-Pugh class B in 57 cases. The treatment schedule included, for each lesion, 6-14 therapeutic sessions performed once or twice weekly. The total amount of alcohol administered ranged 10 to 110 ml (mean: 36 ml). All patients were followed after therapy with clinical examinations, laboratory tests, and imaging studies performed at regular time intervals. The follow-up period ranged 2 to 94 months (mean: 23.6 months). Overall survival rates by the Kaplan-Meier method were 67% at 3 years, 41% at 5 years, and 19% at 7 years. The survival rates of patients with single lesion < or = 3 cm (78% at 3 years, 54% at 5 years, and 28% at 7 years, respectively) were significantly higher (p < .01) than those of the patients with a single lesion of 3.1-5 cm (61% at 3 years, 32% at 5 years, and 16% at 7 years) or multiple lesions (51% at 3 years, 21% at 5 years, and 0% at 7 years). The survival of Child-Pugh A patients (79% at 3 years, 53% at 5 years, and 32% at 7 years) was significantly longer (p < .01) than that of Child-Pugh B patients (50% at 3 years, 28% at 5 years, and 8% at 7 years). A selected group of 70 patients with Child-Pugh A cirrhosis and a single lesion < or = 3 cm had a 3-, 5-, and 7-year survival of 89%, 63% and 42%, respectively. During the follow-up, new lesions appeared in 93 patients. The recurrence rates by the Kaplan-Meier method were 15% at 1 year, 34% at 2 years, 51% at 3 years, 67% at 4 years, 78% at 5 years, 88% at 6 years, and 94% at 7 years. The analysis of the survival curves of the treated patients confirms the effectiveness of PEI in the treatment of HCC. This therapeutic approach is particularly indicated for patients with a single lesion 3 cm or less in greatest diameter, as in these cases the long-term results of PEI are comparable to those reported in the best surgical series published in the literature.