Fibronectin (FN) is reported to enhance particle attachment to macrophages and PMNs. Our previous studies showed that cord plasma FN levels are decreased compared with adult levels and that the opsonic activity against group B streptococci (GBS) of such plasma can be increased by the addition of purified FN. The present studies were designed to determine the role of FN alone and in combination with antibody preparations in providing protection against experimental neonatal GBS infection in a rat model. FN administration alone did not protect against type III GBS infection (untreated 33% survival, n=18; vs treated 29%, n=17). When FN was combined with a polyclonal human IgG preparation modified for intravenous use (IGIV), increased protection was observed (untreated 24% survival, n=17; IGIV 29%, n=17; IGIV+FN 48%, n=31). The enhanced protection observed with a combination of FN and antibody was more impressive when a murine monoclonal type III specific IgG antibody was employed (untreated 0%, n=31; FN 14%, n=29; IgG 17%, n=24; FN+IgG 62%, n=29). FN also enhanced protection by low dose monoclonal IgM antibody (untreated 5%; FN 26%; IgM 18%; FN+IgM 78%). Surprisingly, FN also significantly enhanced protection mediated by an IgA type III monoclonal (untreated 36%, IgA 42%, FN+IgA 65%). These studies indicate that FN interacts with antibody of IgG, IgM and even IgA isotype in host defence. Optimal immunotherapy of neonatal group B disease may involve the adminstration of both antibody and FN.