Positive inspiratory pressure- (PIP) ventilated, isolated rat lungs become edematous when perfused at rates approximately the normal cardiac output. The study was conducted to test the hypothesis that high peak inspiratory pressures contribute to the edema development. Five isolated lungs were perfused at a rate of 24.4 +/- 2.2 ml.min-1.100 g body wt-1 with 40% whole blood (diluted with saline containing 4.0 g/100 ml bovine serum albumin) and ventilated with peak pressures ranging from 0 to 20 mmHg. The lungs exhibited edema at PIP values > 9.3 mmHg. The stable pulmonary vascular pressure and resistance suggested that the edema may have resulted from a PIP-induced increase in microvascular permeability. In a second study, the stability of the preparation was evaluated during a 3-h test period. Seven lungs were ventilated at a peak inspiratory pressure of 8.0 mmHg and perfused at 26.8 +- 1.7 ml.min-1 x 100 g body wt-1. Microvascular integrity was maintained for approximately 2 h as indicated by filtration coefficient measurements of 0.175 +/- 0.068, 0.197 +/- 0.066, and 0.169 +/- 0.067 g.min-1 x mmHg-1 x 100 g-1 at 25, 70, and 115 min, respectively, after initiation of the study. The results suggest that isolated rat lungs perfused at rates that parallel normal rat cardiac output and ventilated at low peak inspiratory pressures provide a viable mechanism for evaluation of the pathophysiology of microvascular injury.