Prostaglandin E1 (PGE1) was compared to placebo in a 100-patient (50 PGE1, 50 placebo) randomized, double-blind, clinical trial to determine whether PGE1 therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused through a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 PGE1 and 24 placebo patients had died. Total deaths judged to be related to the syndrome were 32 and 28 in the PGE1 and placebo groups respectively at six months. We conclude that PGE1 did not enhance survival in patients with established ARDS. PGE1 augmented the hyperdynamic circulation of these patients by reducing systemic and pulmonary vascular resistance, which resulted in a reduction of blood pressures and increased stroke volume, cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observed with PGE1 therapy. PGE1 was associated with an increased incidence of diarrhea (six patients in the PGE1 group vs one in the placebo group, p less than 0.05). Other adverse effects included hypotension (ten patients in the PGE1 group vs seven in the placebo group), fever (six patients in the PGE1 group vs three in the placebo group), and non-fatal dysrhythmias (ten in the PGE1 group vs five in the placebo group).