Taking advantage of the compulsory annual medical check-up at the Central Institute of Health, Japan National Railways, hepatitis B seromarkers were tested in male employees at work and their "dead and alive" status was followed for more than 6 years for their prognostic significance. Two prospective studies were carried out. In the first study, two groups (cohorts) of males age 40 to 55 years were tested in 1973 and 1978, respectively, for HBsAg and anti-HBs. The relative risk of dying from primary liver cancer in HBsAg-positive carriers (n = 126) as compared to the controls who were negative for both HBsAg and anti-HBs (n = 5,322) was 30.03 and significantly high, whereas those positive for anti-HBs (n = 1,470) had no increased risk of dying from primary liver cancer or from other liver diseases. The follow-up period ranged from 6.5 to 11.5 years, averaging 8.5 years. In the second study, three male cohorts of the same ages were tested for HBsAg and HBeAg/anti-HBe (micro-Ouchterlony method) in 1977, 1978 and 1979, respectively. There were 513 HBsAg-positive carriers among 25,547 examinees, who were followed for an average of 7.3 (6 to 8) years. Among these HBsAg carriers, those who were positive for HBeAg on entry had the highest risk of dying from primary liver cancer (relative risk, 50.25) and from other liver diseases (78.06), followed by those negative for both (28.95 and 21.78, respectively) and those positive for anti-HBe (9.47 and 6.43) when compared with 25,034 noncarriers.(ABSTRACT TRUNCATED AT 250 WORDS)