To test the hypothesis that increased proliferative capacity of cells in a liver remnant is a risk factor for tumor recurrence in patients who have undergone liver resection for hepatocellular carcinoma, DNA flow-cytometric measurement and cell-cycle analysis of the nontumor parts of resected hepatocellular carcinomas (tumor size < 5 cm) were performed. The disease-free survival rates 1, 2, 3 and 4 yr after surgery were 64%, 58%, 43%, and 36%, respectively. Proliferative capacity (fractions of synthetic, postsynthetic and mitotic phases) of the nontumor parts, irrespective of liver pathology, was higher than that of normal liver and statistically lower than that of tumor parts from resected hepatocellular carcinoma specimens. Livers with chronic active hepatitis (+) and with hepatocyte dysplasia (-) had significantly lower proliferative activity than did those with chronic active hepatitis (-) and with hepatocyte dysplasia (+), respectively [corrected]. We saw no significant difference in proliferative capacity between patients with and without cirrhosis. Disease-free-survival analysis showed that the presence of liver pathology (hepatitis B infection, cirrhosis, chronic active hepatitis and hepatocyte dysplasia) was not the factor linked to tumor recurrence in the liver remnant and that a marked increase in proliferative capacity (> or = 18%), regardless of liver pathology, was the risk factor linked to tumor recurrence after liver resection. We conclude that there is some degree of increased proliferative capacity in the nontumor parts of resected hepatocellular carcinomas and that a marked increase in the proliferative capacity (> or = 18%) of the nontumor part is a significant risk factor in predicting tumor recurrence in the liver remnant after liver resection.