The authors studied the effects of vasodilator treatment with either hydralazine or minoxidil on gas exchange and lung water accumulation over a 5-h period in canine oleic acid-induced pulmonary edema. Thirty dogs were given intravenous oleic acid 1 day prior to study to produce a stable, diffuse lung injury. On the day of study, one group of animals was given minoxidil, a potent systemic and pulmonary vasodilator. A second group was given hydralazine, a potent systemic vasodilator but weak pulmonary vasodilator, and a third group was not treated. Hemodynamic and gas exchange variables were assessed prior to treatment, and again after 5 h of treatment. Both drugs caused an increase in cardiac output and a decrease in peripheral vascular resistance. Minoxidil increased venous admixture from 17 ± 4 to 55 ± 6% (P< 0.05), whereas hydralazine-treated dogs had a smaller increase, from 26 ± 5 to 47 ± 6% (P< 0.05), and untreated animals did not show a significant change. Lung water increased 27 ± 12% in the untreated animals over the course of the study, 43 ± 18% in the hydralazine animals, and 60 ± 16% (P< 0.05vs.untreated) in the minoxidil animals. The authors conclude that adverse effects may result from peripheral vasodilators in animals with permeability pulmonary edema, but the extent and severity of these effects may vary, depending on the drugs' effects on the pulmonary circulation.