Hepatitis B e antigen (HBeAg) and antibody (anti-HBe) were studied by radioimmunoassay in consecutive series of 145 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 389 patients with HBsAg-positive chronic liver disease and 194 patients with HBsAg-positive hepatocellular carcinoma, and compared between male and female subjects. The male to female ratio increased from 1.2 in asymptomatic carriers to 6.3 in chronic liver disease and 9.8 in hepatocellular carcinoma. Abnormal SGPT was much more frequently seen in male carriers than in females (p less than 0.01). Contrary to female patients with chronic liver disease, the positive rate for HBeAg in males is lower and tended to decrease with increasing age. It is postulated that male patients with chronic hepatis B virus infection might have higher HBeAg clearance ability that resulted in more frequent hepatitis B virus DNA integration and subsequent development of hepatocellular carcinoma. However, the ultimate mechanism regulating this difference awaits further study.