Aspiration or ingestion of contaminated amniotic fluid or vaginal secretions has been suggested as a cause of systemic group B streptococcal (GBS) infection in the neonate. Suckling rat studies disagree on whether systemic disease will develop after an oral challenge of GBS. Our goal was to determine if systemic GBS disease would occur following oral colonization in the suckling rat and the effect of bacterial, host and environmental factors. Suckling rat littermates received oral inoculation on one of the first four days of life with varying doses and strains of GBS. Studies confirmed gastric inoculation without aspiration. Mortality and bacteremia decreased with age, increased with dose, varied with strain, and increased with asphyxia. Autopsy confirmed sepsis, intestinal colonization, meningitis, and pneumonia. Bacteremia was associated with an abnormal immature: total neutrophil ratio at 24hr, thrombocytopenia at 48hr, and neutropenia at 72hr after inoculation. GBS can cause systemic infection in the host after oral colonization which appears age-, dose, strain-, and environment-dependent. Evaluation of GBS entry in the susceptible host may facilitate therapies directed toward preventing mucosal invasion.