In the present study, we investigated the association between hepatocellular carcinoma (HCC) and hepatitis B virus infection (HBV), blood transfusion and drinking and smoking habits by comparing 124 HCC cases and 250 controls. We confirmed a very high relative risk (RR), i.e. 31.0 (P less than 0.001), among persons who were positive for serum hepatitis B surface antigen (HBsAg). However, the prevalence of serum HBsAg positives among our cases was only 21%, about half of those reported earlier, indicating a role of other etiological factors. Those who have a history of blood transfusion showed a significantly elevated RR of 3.0 (P less than 0.001) or 4.9 (P less than 0.001), and most of them (85%) were non-carriers of HBV. Thus, the past history of blood transfusion is an important risk factor among the Japanese. Unidentified non-A, non-B hepatitis viruses in transfused blood probably play a significant role in causing HCC. We estimated that 15% of male HCCs were attributable to blood transfusion. A positive relationship between alcohol consumption and HCC was detected, particularly among HBsAg-negative subjects with no history of blood transfusion who had drunk heavily in their younger years. RR estimates were not great (e.g., heavy drinkers: 2.5), but a substantial proportion of HCC may be attributed to drinking because of common drinking habits among Japanese males. Smoking was also found to have a positive association, but the relationship at a young age was less clear, and further investigation is needed to clarify the etiological role of smoking.