Immunization of mothers during pregnancy may be an effective means of providing protection to infants during the first months of life against many pathogens. Previous studies have identified factors that influence the transfer of immunoglobulin across the placenta, including the time of vaccination during pregnancy and isotypes of specific immunoglobulins. By studying antibodies to Haemophilus influenzae type b polysaccharide (Hib-PS) in 26 pairs of maternal-cord sera obtained from unimmunized healthy women and 22 pairs of maternal-cord sera from women immunized with one of three different Hib vaccines, we have found that the immunoglobulin transfer is also dependent on the V region of antibodies. Anti-Hib-PS derived from the VκII gene 'A2' was transferred about ten times more efficiently to the fetus than other anti-Hib-PS antibodies (20% vs 1-2%). It was found that antibodies derived from the A2 Vκ gene are primarily IgG whereas other antibodies are preferentially associated with the IgM isotype. The potential association between the antibody V region with preferential placental transfer should be considered for future studies involving maternal immunization.