In order to evaluate the roles of hepatitis B virus (HBV) and hepatitis C virus (HCV) and their clinical significance in Asian-American and Caucasian patients with hepatocellular carcinoma (HCC) in the USA, 110 HCC patients, seen in a community-based teaching hospital in the Los Angeles area over a 10 year period, were enrolled. Seventy-nine (72%) patients were Asian-American and 31 (28%) were Caucasians. Of the 110 HCC patients, 69 (63%) were positive for serum hepatitis B surface antigen (HBsAg), 26 (24%) were positive for serum antibody to hepatitis C virus (anti-HCV), five (all Asian-Americans) were positive for both markers; 11 (10%) patients had a history of alcoholism. HBsAg was detected in 63 (80%) Asian-American patients, significantly higher than in the six (19%) Caucasian HCC patients (P < 0.01). Anti-HCV was detected in 10 (32%) Caucasian and in 16 (20%) Asian-American HCC patients (P > 0.05). Among Asian-American HCC patients, anti-HCV was more prevalent in those who were HBsAg-negative than in the HBsAg-positive patients (69 vs 8%; P < 0.01). A history of alcoholism was obtained in nine (29%) Caucasian HCC patients, significantly higher than in the two (3%) Asian-American HCC patients (P < 0.05). Comparing HCC patients with positive HBsAg and with anti-HCV, HBsAg-positive HCC patients were younger, Asian-Americans and predominantly male; 38% had a family history of liver disease. In contrast, anti-HCV-positive HCC patients were older by nearly a decade and 46% had a history of blood transfusion. Using a stepwise logistic regression analysis, Asian race and patient age < 50 years were found to be independent predictors for HBsAg-positivity, while a history of blood transfusion was the only predictor for anti-HCV-positivity in HCC patients. There was no significant difference in the rate of cirrhosis, serum levels of alpha-fetoprotein and survival between HBsAg-positive and anti-HCV-positive HCC patients. In conclusion, chronic HBV infection was the major aetiological factor in Asian-American HCC patients, while chronic HCV infection and alcoholism were major aetiological factors in Caucasian HCC patients in the USA.