Oleic acid (OA) injection into the lungs of dogs produces pulmonary edema and decreased cardiac output, and the result is combined hypoxic and stagnant hypoxia. Prostacyclin (PGI2) has some effects that may be beneficial in the alleviation of hypoxia. We studied 18 anesthetized dogs that were divided into three groups: (1) Six dogs acted as controls and did not receive OA or PGI2, (2) six dogs received OA but no PGI2, and (3) six dogs were first given OA and 1 hour later an infusion of PGI2 (100 ng/kg/min) was started and continued for 4 hours. All dogs were killed at the end of the study and their lungs were removed for weighing and preparation for microscopic examination. Compared with controls, OA caused a low cardiac output, high systemic and pulmonary vascular resistance, and increased right-to-left intrapulmonary shunt. The group that received OA and PGI2 demonstrated a well-maintained cardiac output and a low systemic vascular resistance. Right-to-left intrapulmonary shunt, however, increased in these dogs compared with the dogs not given PGI2. All animals given OA had similar wet/dry lung weights and histologic appearances. Our results suggest that the only beneficial effect of PGI2 in OA-induced lung injury is to improve the stagnant hypoxia, but this is associated with an aggravation of the hypoxic hypoxia. The result of these competing effects appears to be a mild overall improvement in oxygen delivery as suggested by the slightly higher mixed venous PO2 in the group that received PGI2.