BACKGROUND Pulmonary dysfunction and right heart failure are still a common clinical problem after single lung transplantation. METHODS In this study we investigated the pulmonary vasodilatory properties of prostaglandin E1 in pigs during the first 4 hours after left lung allotransplantation. With the use of extracorporeal circulation and total right heart bypass, the right and left pulmonary arteries could be individually perfused and the drug effect in each lung separately analyzed either at equal blood pressures or at equal blood flows in the pulmonary arteries. Twelve animals received in a randomized double-blind fashion either saline solution or an increasing prostaglandin E1 infusion (10, 25, 50, and 100 ng/kg/min; 15 minutes each). After a drug-free period of 75 minutes, the infusion schedule with 25, 50, and 100 ng/kg/min was repeated. RESULTS During the first part of the study the highest dose of prostaglandin E1 decreased the mean systemic arterial pressure by 25%, but an almost similar decrease occurred in the control animals. During the second infusion period a 28% decrease was observed only in the animals treated with prostaglandin E1. None of the infusions was able to decrease pulmonary vascular resistance. Instead prostaglandin E1 diverted two thirds of the pulmonary blood flow toward the native lung, and this diversion manifested itself as an earlier improvement of the arterial oxygen tension in the drug-treated animals. The end-tidal carbon dioxide values measured from each lung corresponded to those from the common expiratory limb of the system, but there was a distinct gradient in the range of 14 to 20 mm Hg between the arterial and end-tidal carbon dioxide values. CONCLUSIONS We conclude that prostaglandin E1, in doses tolerated by the systemic circulation, is ineffective in the treatment of the increased pulmonary vascular resistance after single lung transplantation.