To combat hepatitis B virus (HBV) infection in Taiwan, a mass immunoprophylaxis program was launched on July 1, 1984, aiming first at prevention of chronic HBV carriage from perinatal mother-to-infant infection. In the first 15-month period, 352,721 (78%) of 450,585 pregnant women were screened for hepatitis B surface antigen (HBsAg); HBsAg was present in 62,359 (18%), with 50% of them categorized as highly infectious. Infants born to HBsAg-positive women were given 5 micrograms of a plasma-derived hepatitis B vaccine at ages 1, 5, and 9 weeks, with a booster at age 12 months. Infants of highly infectious carrier mothers received an additional 0.5 mL of hepatitis B immune globulin within 24 hours after birth. The coverage rate of the hepatitis B immune globulin was 77% in 27,375 infants born to highly infectious mothers, and that of the first, second, third, and the fourth doses of vaccine was 88%, 86%, 84%, and 71%, respectively, in infants of 55,620 carrier mothers. The reported untoward reactions to immunization were negligible. We conclude that a mass hepatitis B vaccination program is feasible in hyperendemic areas such as Taiwan; this should be a significant step toward the effective control of HBV infection in these areas.