Since the role of prostaglandins (PGs) in the response of the lung to pulmonary microembolism is unclear, this study examined the effects of indomethacin (INDO), an inhibitor of PG synthesis, on pulmonary hemodynamics and lung fluid balance in normal sheep and in sheep subjected to pulmonary microembolism. Anesthetized, ventilated ewes were given either INDO (5 mg/kg in saline) or emboli (Sephadex G-25, 0.1 ml/kg in saline) via a cannulated jugular vein. Pulmonary arterial (Ppa) and left atrial (Pla) pressures were measured. The ratio of extravascular lung water content to dry weight of the blood-free lung (Qwl/dQl) was measured. Animals were given either INDO 1 hr prior to embolism (Group IV), emboli only (Group III), INDO only (Group II), or were saline controls (Group I). While INDO had little effect in normal animals, Ppa was significantly attenuated in those pretreated with INDO prior to embolism (Group IV) as compared to those embolized only (Group III), and while Qwl/dQl for Group III was significantly elevated compared to Group I, it was not in Group IV. Results suggest that INDO attenuates the pulmonary hypertension caused by microembolism via inhibition of a vasoconstrictor PG, which may in part mediate embolism-induced edemogenesis.