A large-scale, controlled study of universal immunization of newborns against HBV infection has been conducted in the high incidence area of hepatocellular carcinoma, Qidong County of China. This area has a stable population, standardized cancer registration system, and an epidemiological base for measurements of liver cancer prevention by vaccine. Randomization was done on the community level. The vaccination and the control group each will consist of 38,000 children by the end of 1990. It is anticipated that the design will provide high statistical power to detect 50% reduction in the prevalence rate of chronic hepatitis among the vaccinees vs. the controls at 6 to 10 years of age, and 50% reduction in the incidence rate of hepatocellular carcinoma at 35 to 40 years of age. The vaccine used is Hep-B Vax, donated by Merck and Co. through WHO. The vaccine was administered at 0, 1, and 6 months after birth, the dosage of 5 or 2.5 micrograms in the pilot study as used before 1985 and of 5 micrograms dose level during the main study starting from January 1, 1985. About 85% of the cohorts have now entered the protocol. The vaccination coverage during 1984 to 1989 was 98.0% (35,064/35,789). Follow-up of the vaccinees and the age-matched controls at 5 years has exceeded 97%. The cumulative mortality in the vaccinated group up to 1988 was 1.29% (354/27,450). No single death nor serious adverse reaction was found that was associated with vaccination. The use of HBV vaccine at a reduced dose was especially important for the developing countries at the present time in order to achieve widespread immunization. Five-year results of the pilot study of this vaccination project showed that significant protection against HBV infection was achieved with the 5 or 2.5 micrograms per dose regimen plus a booster of 5 micrograms given at 3.5 to 4 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)