We studied the effect of heavy alcohol intake (ethanol intake > or = 80 g/day for > or = 5 yr) on long-term results in 53 patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) who had undergone curative hepatic resection. Cell proliferative activity in the tumor and non-tumorous liver was also assessed by counting argyrophilic nucleolar organizer region-associated proteins (Ag-NOR) in the resected specimens. Twenty patients (20 males, 0 females) were positive for heavy alcohol intake [AI(+)] and 33 (28 males, 5 females) were not [AI(-)]. All patients were positive for HCV antibody and negative for hepatitis B surface antigen. Carcinoma recurred within 3 to 51 postoperative months in 42 (79.2%) of the 53 patients. The median disease-free survival time was 12.6 mo in the AI(+) group and 25.4 mo in the AI(-) group (P < 0.01). The AI(+) group also had significantly poorer survival than the AI(-) group (P < 0.05, 3-year survival rate: 66.7% vs. 93.5%). HCC tumor in the AI(+) group showed significantly increased proliferative activity compared with that in the AI(-) group (P < 0.05, Ag-NOR number: 2.3 +/- 0.8 vs. 1.9 +/- 0.4). However, there was no significant difference between the numbers of Ag-NORs in non-tumorous liver from these two groups (1.5 +/- 0.2 vs. 1.5 +/- 0.2). Patients with heavy alcohol intake should be followed particularly closely, even if they have received curative surgery, since heavy alcohol intake is closely related to a poor postoperative prognosis.