Objective. We compared the diphtheria and tetanus toxoids and bicomponent acellular pertussis vaccine (DTaP) responses in Japanese and United States infants. Design. This was a double-blind, comparative study. Setting. Private pediatric practices in Japan and the U.S. participated. Subjects. One hundred eighty-nine healthy 2-month-old infants were tested. Interventions. Infants were immunized at 2, 4, and 6 months of age. The Japanese formulation (DTaP-J) contained 20 µg of pertussis toxin (PT) and 20 µg of filamentous hemagglutinin (FHA); the U.S. formulation (DTaP-US) contained 23.4 µg of each antigen. Parents used a standard form to record adverse experiences. Serum was obtained before the first immunization, 2 months after the second immunization, and 1 month after the third immunization. Measurements. Differences in DTaP-J and DTaP-US were evaluated in Japanese infants immunized subcutaneously (SC). Differences due to ethnicity and to route of administration were compared in U.S. infants immunized with DTaP-US SC or intramuscularly (IM). An indirect enzyme-linked immunosorbent assay was used to determine immunoglobulin G antibody responses to PT, FHA, and tetanus toxoid. Neutralizing antibody to PT was measured by a Chinese hamster ovary cell assay. Diphtheria antitoxin was assayed by serum neutralization on VERO cells. Results. Statistical differences (P < .05) in adverse events included less fatigue after immunization with DTaP-US compared with DTaP-J. Erythema of more than 2.5 cm was more frequent, but erythema less than 2.5 cm was less frequent in Japanese infants compared with U.S. infants. Fewer Japanese infants were febrile (> 38°C), tired, or irritable. Subcutaneous immunization resulted in a greater frequency of erythema and induration. The DTaP-US resulted in an equivalent response to PT and a greater response to FHA. More Japanese infants demonstrated at least a fourfold response over preimmunization antibody values to FHA. In U.S. infants, antibody responses to the contained pertussis antigens were equivalent after IM and SC administration. Compared with Japanese infants receiving DTaP-J SC, U.S. infants receiving DTaP-US IM had equivalent responses to PT and a greater response to FHA. Conclusions. United States infants receiving an IM injection of a U.S.-produced bicomponent DTaP vaccine produced antibody responses to the contained pertussis antigens at least equal to those of Japanese infants receiving a similar bicomponent DTaP vaccine shown to be effective in older Japanese children.