Although gram-negative sepsis is a major cause of neonatal morbidity and mortality, our understanding of endotoxemia in the neonate has been hampered by the lack of experimental models. Previous studies have suggested neonatal hyporesponsiveness to endotoxin. We studied unanesthetized neonatal lambs which had been exposed to the environment prior to study. These animals demonstrated the classic early phase changes of endotoxemia including pulmonary hypertension which was dependent upon prostanoid production. This model allows further studies of endotoxemia in the neonate.