Through its ability to cause lipid peroxidation, nitrogen dioxide (NO2) may affect the functional properties of both the pulmonary epithelium and endothelium. We evaluated this possibility in 13 mongrel dogs by exposing these animals to 200 or 400 ppm NO2 for 1 h. The changes in pulmonary epithelial permeability (using a radioaerosol technique), FRC, and endothelial function (the removal of radiolabeled serotonin, [14C]5-HT, and prostaglandin E1, [3H]PGE1, from the pulmonary circulation) were measured at 1 h and at 2, 7, or 14 days after NO2 exposure. In another six dogs, we evaluated changes in cell population and albumin in bronchoalveolar lavage (BAL) fluid caused by NO2. In the first two days after NO2 exposure, focal pulmonary edema was documented on microscopy, radioaerosol clearance was delayed, and FRC decreased slightly. BAL showed a marked increase in albumin, but the removal of trace amounts of 5-HT and PGE1 by the endothelium was not altered. All physiologic abnormalities returned to normal with time.