To investigate risk factors for hepatocellular carcinoma (HCC) in Italy--a country with medium (south: 5% to 10%) to low (north: 1% to 2%) incidence of hepatitis B virus (HBV) infection--we studied 646 consecutive patients: 58 chronic active hepatitis (CAH), 428 cirrhosis, and 160 HCC, 49% from Southern and 51% from Northern Italy. Hepatitis B surface antigen (HBsAg) was positive in 41.4% of the CAH, in 23.1% of cirrhotic patients, and in 26.2% of HCC. In the latter, HBV DNA assay increased the number of subjects with active HBV infection by about 12%. Alcohol abuse was evenly distributed in all three categories of HBV markers. Males were preferentially affected. The HCC was superimposed on cirrhosis in more than 90% of patients. Our data suggest that, in our epidemiologic setting, different factors (HBV, non-A, non-B agents, alcohol) may cooperate in the development of HCC, mainly through their potential for causing cirrhosis.