Because PGE1 previously has been reported to increase survival of patients with ARDS, we evaluated physiologic effects and side effects of PGE1 in a prospective open-label study of patients with ARDS. Seventeen patients with ARDS who did not have significant renal or hepatic dysfunction received PGE1 by continuous central venous infusion (30 ng/kg/min). Seventeen control patients with ARDS without renal or hepatic dysfunction who had similar APACHE II and ARDS scores and causes of ARDS did not receive PGE1. Prostaglandin E1 significantly decreased the SVRI and oxygen extraction ratio. Concentrations of total and polymorphonuclear leukocytes, but not platelets, increased significantly during PGE1 infusion, but did not change in control patients. There was no change in the Do2I and Vo2I during the course of the PGE1 infusion. There were no differences in Do2I and Vo2I during PGE1 infusion between survivors and nonsurvivors. Prostaglandin E1 was infused for a mean of 5.9 +/- 1.8 days (+/- SD) and was discontinued on ten occasions in seven patients because of supraventricular dysrhythmias (n = 4), hypotension (n = 3), thrombocytopenia (n = 3), and cardiac arrest (n = 2). Nonsurvivors had PGE1 discontinued prematurely more frequently than survivors (56 percent [5/9] vs 25 percent [2/8], respectively). The prevalence of multiple-system organ failure and the in-hospital mortality of both PGE1-treated and control patients were not different. Although PGE1 causes significant systemic vasodilation and possibly decreased intrapulmonary polymorphonuclear leukocyte sequestration, PGE1 does not influence multiple-system organ failure or mortality of patients with ARDS without renal or hepatic dysfunction.