Current evidence suggests that pulmonary edema accompanying human sepsis may result either from changes in the serum oncotic and hydrostatic pressures or an increase in the permeability of the pulmonary microvasculature. In this study, we compared the "clearance" of injected 131I-labeled human serum albumin from blood to bronchoalveolar secretions in intubated patients with pulmonary edema secondary to sepsis or myocardial infarction. A significantly increased mean +/- SE clearance of the radionuclide was seen in patients with sepsis (0.34 +/- 0.03 ml per hour) compared to those with myocardial infarction (0.043 +/- 0.008 ml per hour) (P less than 0.001), although both groups had similar degrees of edema on chest radiographs. Because the patients with sepsis had no severe decrease in serum oncotic pressure (18.4 +/- 5.0 mm Hg) or evidence of left heart failure, as determined by the pulmonary wedge pressure (11.0 +/- 6.8 mm Hg), we concluded that the genesis of the pulmonary edema in sepsis was due to an increase in pulmonary microvascular permeability, as measured by the increased clearance of 131I-labeled human serum albumin.