Requirements for complement and antibody in neutrophil-mediated killing of serotype IV and V group B streptococci were investigated. Neutrophils from adults were tested in an opsonophagocytic assay with sera from healthy adults, healthy newborns, and hypogammaglobulinemic, agammaglobulinemic, and C4-deficient patients. For all serum sources, the bactericidal index for both serotypes exceeded 84% after 40 min of incubation. Heat inactivation of sera ablated killing. Blockade of neutrophil receptor FcIII effected a maximum of 16% inhibition of opsonophagocytosis, and FcII receptor blockade demonstrated negligible inhibition. When neutrophil complement receptor 1 or 3 blockade was employed, the maximum inhibition detected was 26%. Simultaneous blockade of complement receptors 1 and 3 effected maximum inhibition levels of 25 and 65% for serotypes IV and V, respectively. Blockade of complement receptor 3 and neutrophil receptor FcIII inhibited opsonophagocytosis by 56% for both serotypes. When serum complement concentrations were restricted, neutrophil-mediated killing diminished but was restored by the addition of hyperimmune rabbit antiserum. These findings suggest that complement and antibody are major participants in the opsonophagocytosis of serotypes IV and V group B streptococci. A low prevalence of carriage or mediation of efficient phagocytosis by interactions of neutrophil complement and Fc receptors may contribute to the rarity of human infections caused by these two serotypes.