Prostaglandin E1 (PGE1) has been reported to improve survival in patients with the adult respiratory distress syndrome (ARDS). However, the effects of this pulmonary vasodilating compound on gas exchange have been little documented. We therefore measured hemodynamics, blood gases, and the distributions of ventilation-perfusion ratios (VA/Q), using the multiple inert gas elimination technique, at baseline and during infusion of PGE1 0.02 to 0.04 microgram.kg-1.min-1 in six patients with pulmonary hypertension secondary to ARDS ventilated with 10 cm H2O positive end-expiratory pressure. PGE1 decreased systemic arterial mean pressure (-16%) and pulmonary arterial mean pressure (-15%) and increased cardiac index (+20%) and heart rate (+11%). Arterial PO2 decreased from 99 +/- 6 to 77 +/- 8 mm Hg (p less than 0.01, mean +/- SEM) with no change in mixed venous PO2 and in O2 consumption. PGE1 increased true shunt from 21 +/- 4 to 32 +/- 5% of total blood flow (p less than 0.01) with no significant modification in the pattern of VA/Q distribution. Thus, in ARDS, pulmonary hypertension is reduced by PGE1 at the price of a deterioration in pulmonary gas exchange. The clinical relevance of these findings remains to be evaluated.