In an autoperfused heart-lung preservation the lungs usually deteriorate earlier than the heart. This study examines the effect of prostaglandin E1 on the lungs in a newly designed autoperfusion model for heart-lung preservation. This model provided constant preload and afterload with stable hemodynamic parameters so that precise changes of lung function could be measured. Lung function was evaluated by the changes of arterial blood gas, pulmonary vascular resistance, pulmonary compliance, and serial biopsies. Eighteen mongrel dogs were divided into two groups. Seven control dogs received no prostaglandin E1. The study group consisted of seven dogs that received continuous infusion of prostaglandin E1 (1, 10, and 40 ng/kg/min) through the pulmonary artery. Attempts to infuse larger concentrations of prostaglandin E1 at 10 to 40 ng/kg/min resulted in ventricular fibrillation in four animals not included in the analysis. In the control group lung function showed good viability up to 5 hours; however, the lungs deteriorated, and lung edema occurred in all experiments after 9 hours. A lower dosage of prostaglandin E1 (1 ng/kg/min) infusion was effective in seven dogs, which prevented lung deterioration, and five of the seven lungs were well preserved for 10 hours with stable arterial oxygen tension, pulmonary vascular resistance, and pulmonary compliance. Ventricular fibrillation occurred at dosages of 10 to 40 ng/kg/min of prostaglandin E1 in four dogs. These dogs therefore were excluded from the analysis. In conclusion, prostaglandin E1 appears to have a beneficial effect on autoperfused heart-lung preparation.