Twelve infants, born to mothers with hepatitis B virus infection, were inoculated within 7 days of birth with immune serum globulin containing antibody to hepatitis B surface antigen (HBsAg) titers of 1:32 to 1:64 as measured by passive hemagglutination. Six of nine infants (66.7%) born to HBsAg-positive carrier mothers became HBsAg-positive within 3 mo of age. In addition, two of three treated infants born to mothers with acute hepatitis B during the delivery period also developed HBsAg. The hepatitis e antigen was detected in four of five carrier mothers and in two mothers with acute hepatitis, whose infants subsequently became HBsAg positive. In addition, hepatitis B-specific DNA polymerase activity was detected in the seven HBsAg-positive mothers who transmitted the virus to their infants. All eight infants have remained persistently HBsAg positive. Thus, the immune serum globulin containing low-titer antibody to HBsAg is not protective when given to infants born to HBsAg carrier mothers or to mothers with acute hepatitis B during the delivery period.