Prostaglandin E1 (PGE1, Prostin VR) in doses of 30 ng/kg . min was studied in two series of severely ill surgical patients with adult respiratory distress syndrome (ARDS). First the drug was administered in an initial trial in six patients; then a prospective, randomized, blinded trial was conducted in 10 studies on nine patients. PGE1 markedly decreased pulmonary artery pressure, pulmonary and systemic vascular resistance indexed, and venous pressures, while increasing cardiac output, arterial PO2 (PaO2), oxygen delivery, and oxygen consumption when compared with the baseline preinfusion control values and with the response of the placebo-treated control series. The PGE1 responses were greater in patients whose ARDS was primarily attributed to the postoperative state with or without sepsis and least in patients with cirrhosis. The data are consistent with the concept that the drug reduces vasoconstriction primarily in the pulmonary circulation but also in the systemic circulation; improved PaO2 usually follows the hemodynamic effect. We conclude that PGE1 may be a useful adjunctive therapy for ARDS.