Despite the serious pulmonary manifestations of early onset group B streptococcal (GBS) sepsis, it is not known whether the organism distributes into lung tissue and whether adverse pulmonary hemodynamic abnormalities relate to an interaction between the organism and target cells in the pulmonary vascular bed. Accordingly, this study evaluated the distribution and fate of GBS in the lung, liver, and spleen of anesthetized infant piglets and in isolated, salt solution-perfused piglet lung preparations. GBS were radiolabeled with111Indium-oxine and infused at a dose of 108organisms/kg/min for 15 min into anesthetized piglets ranging in age from 5-10 d. Forty-five min after termination of the infusion, animals were killed and specimens of lung, liver, spleen, and blood were excised and the relative deposition and viability of GBS were determined. Most of the recovered bacteria were detected in the lung (53.2 ± 3.9%) followed by the liver (41.4 ± 2.0%) and spleen (2.2 ± 0.38%). GBS detected in the blood was estimated to be only 3.2 ± 1.0% of the infused dose. Viability of GBS was least in the lung (21.4 ± 2.6%) relative to the liver (45.7 ± 11.2%) and spleen (83.4 ± 19.5%). After a 60-min GBS infusion, transmission electron microscopy localized the organism within pulmonary intravascular macrophages in the lung; there was no evidence for bacterial interaction with either neutrophils or endothelial cells. In the liver, GBS was found exclusively in Kupffer cells. In isolated piglet lungs perfused at a constant flow rate with blood-free physiologic salt solution, GBS (106to 108organisms/mL) provoked concentration-dependent increases in pulmonary vascular resistance. Transmission electron microscopic examination of isolated lungs indicated that GBS was localized within pulmonary intravascular macrophages, again with no apparent intractions between the organism and other cellular residents of the pulmonary vascular bed. These results indicate that GBS distributes into lung and liver where resident intravascular phagocytes, possibly pulmonary intravascular macrophages and Kupffer cells, respectively, contribute to killing of the organism. In addition, because GBS evokes pulmonary hypertension in isolated piglet lung preparations, it appears that cardiopulmonary disturbances in the intact animal could be initiated by a direct interaction between GBS and resident lung cells without obligatory participation by other organ systems.