To examine the development of pulmonary edema during experimental renal dysfunction, left atrial pressure was altered in 14 mongrel dogs divided into two groups. Group 1 was composed of seven control animals, and Group 2 was composed of seven animals with surgically induced renal failure (1 week of bilateral ureteral ligation). Data were obtained at two levels of matched transmural pulmonary vascular pressure (defined as mean left atrial pressure less serum protein osmotic pressure). In the animals with renal dysfunction, extravascular lung water (EVLW) (thermal-green dye technique) was higher at moderately (-1 to -2 mm Hg) and severely elevated (11 to 12 mm Hg) vascular driving pressures (11.5 +/- 1.2 cc/kg vs 10.6 +/- 0.8 cc/kg and 14.8 +/- 1.3 cc/kg vs 13.0 +/- 1.9 cc/kg, respectively, both P less than 0.05 vs control). Because protein osmotic pressure was lower in the renal failure group (15.0 +/- 1.8 mm Hg vs 18.4 +/- 1.4 mm Hg, P less than 0.05), greater accumulations of extravascular lung water occurred at lower levels of left atrial pressure (14.2 +/- 1.4 mm Hg vs 17.1 +/- 1.2 mm Hg, P less than 0.05; 26.8 +/- 2.6 mm Hg vs 29.5 +/- 2.3 mm Hg, P less than 0.01). In addition, when the ratio of EVLW/PBV (pulmonary blood volume) was examined in both groups at each stage of the experiment, the ratio was greater in the Group 2 animals at each elevated pressure, suggesting increased permeability with renal dysfunction. In conclusion, pulmonary edema formation occurs at lower left atrial pressures in the setting of sustained renal dysfunction, this phenomenon can be partially explained by lower protein osmotic pressure though altered pulmonary microvascular permeability may contribute to edema formation.