We studied the effect of left atrial pressure (LAP) elevation on the formation of pleural effusion in unanesthetized sheep. We prepared the animals by placing catheters in the left atrium, pulmonary artery, femoral artery, and vein. We also placed a balloon catheter in the left atrium. After a recovery period of at least 1 wk, we measured LAP, pulmonary artery pressure (PAP), systemic arterial pressure, systemic venous pressure, cardiac output, plasma protein concentration, and plasma colloid osmotic pressure (pi c). We calculated capillary pressure (Pc) as 0.5(PAP - LAP). We then elevated LAP such that Pc-pi c was between -10 and 19.5 mmHg for 6-24 h. At the end of the experiment, we killed the sheep and measured the volume and protein concentration of the right pleural effusion. We also determined the extravascular fluid to blood free dry weight of the right lung. We found that pleural effusions and pulmonary edema formed when Pc-pi c greater than 5 mmHg. We also found that the pleural effusion volume correlated with the amount of pulmonary edema. Our data show that elevated LAP may cause pleural effusions, but only after pulmonary edema has developed.