For early detection of hepatocellular carcinoma (HCC), real-time ultrasonography (US) was performed prospectively in 528 patients, including 236 with cirrhosis, 81 with chronic hepatitis, 168 asymptomatic hepatitis B surface antigen carriers, and 43 with a family history of HCC. Simultaneous measurement of serum alpha-fetoprotein (AFP) level was also done. In addition, 233 patients had regular controls at 3- to 6-month intervals, with an average follow-up period of 1.4 years. On initial screening, a total of 17 patients were found to have HCC: 13 in the cirrhotic group, 3 in the HCC family group, and 1 in the asymptomatic carriers. Of these HCCs, 7 were smaller than 3 cm, 6 were between 3 to 5 cm, and 4 were larger than 5 cm. In patients with tumors smaller than 5 cm, the AFP levels were normal in 46.2%, between 20 to 400 ng/ml in another 46.2%, and only 7.6% were over 400 ng/ml. On follow-up, another seven patients, all in the cirrhotic group, were found to have HCCs varying from 1.6 to 4.7 cm; three of them had normal serum AFP level. The authors conclude that real-time US is more sensitive than AFP assay in early detection of HCC, and the high-risk subjects should receive this procedure at regular intervals.