We have investigated the opsonic and protective effects of fibronectin (FN) against type III group B streptococci. When used by itself, the FN failed to promote actual internalization of group B organisms. The addition of FN to group B streptococci that had been preopsonized in an immunoglobulin preparation modified for intravenous use ( IgIV ) or a type-specific, murine monoclonal antibody of IgG isotype markedly enhanced interaction with human polymorphonuclear leukocytes (PMN). A similar enhanced effect was observed when the FN was combined with type-specific monoclonal antibody preparations of IgM and, surprisingly, IgA isotype. Preincubation experiments indicated that the major effect was upon the PMN rather than directly on the bacteria, but we could not demonstrate an effect of FN on cell surface receptors for the Fc fragment of Ig or C3b using rosetting techniques. In addition to enhancing the in vitro opsonic activity of Ig, the FN significantly increased the protective effect of the polyclonal and monoclonal Ig preparations in an animal model of neonatal group B streptococcal disease. Thus, FN appears to have a critical role in the host defense mechanisms against group B streptococci.