Seventy-three infants born to HBeAg positive HBV carrier mothers were protected from neonatal HBV infection with our standard prevention schedule consisting of two doses of HBIG (0,2 mo) and three doses of HBV vaccine (2, 3, 5 mo). In 62 infants who successfully responded to HBV vaccine with a titer of anti-HBs greater than 2(3), anti-HBs titer was monitored for as long as 48 months (25.6 +/- 11.0 mo) and found to decrease as follows: 5.1 +/- 1.7 at 12 mo., 4.5 +/- 1.8 at 18 mo., 4.2 +/- 1.8 at 24 mo., 4.0 +/- 1.6 at 30 mo., 3.7 +/- 1.7 at 36 mo., 3.2 +/- 2.0 at 48 mo. During the follow-up period, eight HBV events (11.9%) were demonstrated: one case showed an increase of anti-HBs, three showed a reappearance of anti-HBc alone, three showed a reappearance of anti-HBc with increase of anti-HBs, and one became a chronic HBV carrier. All infants were further divided into three groups by their maximal response of anti-HBs to HBV vaccine: Group I (greater than or equal to 2(6)), Group II (2(3)-2(5)), and Group III (2(2) greater than or equal to). Group I sustained a higher titer from 12 to 30 months of age and had less HBV events than G-II and G-III. Our study suggests that acquisition of a high titer of anti-HBs is important in long-term prevention of HBV infection as well as in the neonatal period in infants born to HBeAg positive HBV carrier mothers.