During our earlier saralasin infusion study in hypertensive patients, we found a drug-induced rise in arterial oxygen tension (PaO2) associated with unchanged mixed venous PO2 or the PaCO2 and unrelated to cardiopulmonary hemodynamic changes. To test the hypothesis that saralasin improved pulmonary mechanics, blood gases, lung mechanics, lung volumes, diffusing capacity, and distribution of ventilation were analyzed and cardiac output (CO) measured in 12 normotensive men with chronic pulmonary disease before and during a 2 1/2 hour infusion of Saralasin (5 micrograms/kg/min). The PaO2 increased from a mean of 63 +/- 3 (SEM) to 70 +/- 3 mm Hg (p less than 0.001), while the CO decreased from 6.81 +/- 0.52 L/min to 6.18 +/- 0.48 L/min (p less than 0.005). The change in (delta)CO correlated with delta PaO2 (r = -0.67, p less than 0.05). Total systemic vascular resistance rose from 1,201 +/- 134 to 1,353 +/- 147 dynes X sec X cm5 (p less than 0.001). The PaCO2 and other measurements remained unchanged. We conclude that saralasin raised the PaO2 not by changing pulmonary function or mechanics, but by redistributing pulmonary blood flow and improving the ventilation-perfusion relationship.