Prostaglandin E1 (PGE1) administration is a useful therapeutic measure for short-term maintenance of ductal patency in patients with obstructions to pulmonary or systemic blood flow. Such treatment is not without complications, however, and a report of three infants from our institution with abnormalities of the pulmonary microvasculature after varying periods of PGE1 therapy was recently published (Heffelfinger et al., Pediatr Pathol 1987;7:165-73). The vascular abnormalities appeared to be temporally related to the PGE1 administration. To test this hypothesis, we investigated the effects of PGE1 in newborn beagles by infusing PGE1 for periods of up to 21 days in four experimental pups. Two control pups were infused with saline for the same period of time. Five of the animals developed respiratory infection during the course of the infusions. One PGE1-treated pup was not infected. Both the PGE1- and saline-treated pups had bronchopneumonias of similar severity; however, pulmonary arteritis occurred only in the PGE1-treated pups. The severity of the arteritis varied with the amount of pulmonary parenchymal inflammation and not with the duration of PGE1 administration. Inflammatory and vascular lesions were found in organs other than the lung only in two pups receiving longer courses of PGE1 treatment. We conclude that systemic PGE1 infusion at therapeutic levels plays a role in the development of arterial lesions in small muscular arteries and that this is potentiated by the presence of infection.