An efficacy trial of hepatitis B immune globulin in the prevention of perinatal transmission of hepatitis B virus infection was conducted in Los Angeles. Ten infants born to hepatitis B surface antigen (HBsAg)-and hepatitis B e antigen (HBeAg)-positive carrier mothers as well as 4 infants born to mothers with acute hepatitis B in the third trimester of pregnancy received hepatitis B immune globulin without randomization. Twenty infants born to HBsAg- and antibody to hepatitis B e antigen (anti-HBe)-positive carrier mothers were randomized to receive hepatitis B immune globulin or a placebo. All infants were followed for up to 18 mo. Four infants (2 born to HBeAg carrier mothers, 1 to an anti-HBe carrier, and 1 to a mother with acute hepatitis) became HBsAg-positive carriers, whereas another infant, whose mother was an HBeAg carrier, developed a transient anicteric hepatitis B infection. All infants who became infected did so after 9 mo of age as hepatitis B immune globulin protection waned. In infants born to HBsAg-positive carrier mothers, active immunoprophylaxis with the hepatitis B vaccine must be used in conjunction with hepatitis B immune globulin.