SUMMARY Pulmonary edema which develops during acute myocardial infarction is generally believed to result solely from pulmonary microvascular hypertension. However, patients with myocardial infarction and pulmonary edema occasionally are found to have normal pulmonary wedge pressure. We report data indicating that pulmonary edema develops after coronary artery ligation despite stable microvascular pressure. Four groups of open-chest dogs were studied: (1) nine dogs with left anterior descending coronary artery ligation, (2) seven dogs with sham coronary ligation, (3) seven dogs ligated after beginning an infusion of indomethacin (5 mg/kg per hr), and (4) five dogs ligated after an infusion of the drug's vehicle was begun. Extra vascular lung water and pulmonary blood volume were measured at hourly intervals during the 2 hours before and after coronary ligation or sham ligation. Gravimetric lung water was measured immediately thereafter. Changes of net pulmonary intravascular driving force (the difference of microvascular hydrostatic and oncotic pressure) after ligation or sham ligation were small and comparable in all groups. Pulmonary blood volume did not change in any group. Pulmonary extravascular water volume remained constant in the sham group but rose significantly in the ligated group. Gravimetric lung water also was significantly higher in the latter group. We interpret these results to indicate that factors other than microvascular pressure can mediate the formation of edema during acute myocardial infarction; increased pulmonary microvascular permeability may be responsible. Indomethacin infusion blocked the formation of edema after coronary ligation, even though net microvascular driving force was highest in this group. Infusion of the vehicle alone did not prevent edema. The mechanism by which indomethacin exerts this protective effect is unclear but is probably a result of its inhibition of cyclo-oxygenase or cyclic nucleotide phosphodiesterase. Circ Res 50: 301-309, 1982PULMONARY edema is commonly categorized as "cardiogenic" or "non-cardiogenic," with the implication that the former type is mediated by pulmonary microvascular hypertension, whereas altered endothelial permeability accounts for the development of the latter form (Robin et al., 1972;Staub, 1974aStaub, , 1978. Pulmonary edema which develops in the setting of an acute myocardial infarction (MI) is generally believed to result solely from high pulmonary microvascular pressure, since depressed myocardial contractility, decreased left ventricular compliance, and peripheral venoconstriction commonly raise the pressure of the lesser circulation during acute MI. However, radiographic and clinical signs of pulmonary edema during MI are noted occasionally despite the presence of normal pulmonary wedge pressure (Nixon and Durth, 1968;Lassers et al., 1970; Kostuk et al., 1978;Timmis et