A total 1400 hepatitis B surface antigen-positive Alaska natives, 824 men and 576 women of all ages, were followed up prospectively over a period of 7815 carrier years for the development of sequelae related to chronic hepatitis B virus infection. During the observation period, 20 cases of hepatocellular carcinoma, 14 cases of chronic active hepatitis, 8 cases of cirrhosis, and 1 case of glomerulonephritis developed in this cohort. The annual incidence of hepatocellular carcinoma was 387 per 100,000 for men and 63 per 100,000 for women. The incidence of chronic active hepatitis and cirrhosis was 193 and 107 per 100,000 in men and 158 and 95 per 100,000 in women, respectively. No cases of either essential mixed cryoglobulinemia or necrotizing vasculitis were seen. Sixty of the hepatitis B surface antigen-positive carriers died, with 13 (21.7%) of the deaths due to hepatocellular carcinoma. The leading cause of death in this group was malignant neoplasms compared with accidents in the general Alaska native population.