Hepatitis B vaccine has been recommended for high-risk individuals in the United States for more than a decade. This targeted strategy, however, has failed to control hepatitis B virus (HBV) infection. Universal immunization is being considered as an alternative approach, in particular the inclusion of hepatitis B vaccine with routine childhood vaccinations. Data presented herein demonstrate a high degree of efficacy for hepatitis vaccine with hepatitis B immune globulin in preventing perinatal HBV infection in newborns. Immune response to vaccine was dependent in part on the dose administered, with some enhancement of response if the infant was older at the time of initial injection or if the booster dose was given later. Long-term follow-up showed persistence of vaccine-induced antibody for 5 to 10 years in 90% of immunized infants and adults. Only 3% to 5% of these high-risk individuals had serologic evidence of an HBV infection. None of the infections had been symptomatic and none resulted in a chronic HBV carrier state. Thus, immune responses and efficacy of hepatitis B vaccine in infants were excellent, and immunity and protection against clinically significant HBV infection persisted for at least 5 to 10 years, features essential to success of a program of universal childhood immunization against HBV