We established an experimental animal model of the gastrointestinal colonization and systemic disease following oral challenge of type III group B streptococcal strain in 3-day-old newborn rats. Two type III group B streptococcal strains isolated from the cerebrospinal fluid of septic newborn infants produced colonization in 57-87% of the challenged animals and 13-31% of these colonized animals developed systemic disease. Using this new animal model, we evaluated the effect of orally administered human immune serum globulin on the colonization and systemic disease. This antiserum contained 21 µg/ml of type III group B streptococcal antibody of human IgG class. Animals fed with immune serum globulin developed significantly lower rates of colonization and systemic disease than those of control (albumin or saline) (23 versus l\%,p<0.001 for colonization; 7 versus 31%, p<0.05 for systemic disease). However, rates of the development of systemic disease among the colonized animals were not significantly different between the two groups (33versus43%, p>0.1). These findings suggest that orally administered immune serum globulin is beneficial in the prevention of colonization and systemic disease in this rat model and that this protective effect of oral immune serum globulin occurs primarily at the mucosal level