In an effort to further understand the host defense against group B streptococcus (GBS), we examined 71 human cord sera for their content of type III GBS IgG antibody by enzyme-linked immunosorbent assay and correlated the results with opsonic and protective activity against type III GBS. Most cord sera (67%) containing greater than 0.1 microgram/ml of type III GBS IgG antibody promoted phagocytosis and killing in vitro and protection against type III GBS in neonatal rats. However, 26% of cord sera containing less than 0.1 microgram/ml of type III IgG antibody exhibited similar activity in vitro and in vivo against type III GBS. This opsonic and protective activity was retained in IgG fraction of whole serum, and was not directly associated with complement activity or with fibronectin. Further studies are needed to understand the mechanisms responsible for the opsonic and protective activity of some cord sera against type III GBS that may be independent of antibody to the type-specific polysaccharide antigen.