Prospective study of early detection of hepatocellular carcinoma in patients with cirrhosis. We prospectively monitored 140 cirrhotic patients for the development of hepatocellular carcinoma for 6 yr, using periodical screening by high-resolution convex-array ultrasonography and alpha-fetoprotein. Twenty-eight patients were positive for HBs antigen, 26 patients had received blood transfusions and were negative for HBs antigen and 26 patients had a history of heavy drinking. We detected hepatocellular carcinoma in 40 patients during this period. The overall cumulative incidence of hepatocellular carcinoma in the 6 yr was 39%; the cumulative incidence was 59% in patients with HBsAg, 53% in patients who had had blood transfusions and were negative for HBsAg and 22% in patients who had a history of heavy drinking and who were without HBsAg. Detection of the carcinoma in 85% of these 40 patients was based on results of ultrasonography. Twenty-six of the patients (65%) had a small hepatocellular carcinoma of 2 cm or less. alpha-Fetoprotein levels were lower than 100 ng/ml in 56% of these 40 patients. Patients with cirrhosis are at high risk of developing hepatocellular carcinoma, especially patients with HBsAg or with a history of blood transfusion who are negative for HBsAg. Periodic monitoring by use of ultrasonography in particular is recommended for early detection of hepatocellular carcinoma. 