Anticoagulation during hemodialysis is necessary to prevent clotting of the blood on contact with the dialysis membrane. Heparin is the usual anticoagulant used, but systemic anticoagulation may persist for hours, and hemorrhage is common. We successfully used an infusion of prostacyclin, which has an in vitro half-life of three to five minutes, as the sole anticoagulant in 10 patients on long-term hemodialysis and in one patient undergoing dialysis for acute renal failure (this patient bled severely on three occasions when heparin was used). Prostacyclin was infused intravenously for 10 minutes before dialysis and into the arterial line of the dialyzer during dialysis. We adjusted the rate of infusion into the dialyzer to prevent prostacyclin-induced hypotension. Each patient completed 240 minutes of dialysis and received a total of 423 +/- 91 ng of prostacyclin per kilogram of body weight (mean +/- S.E.M.; range, 56 to 780). Prostacyclin caused no clinically important changes in the intrinsic clotting system, and there were no hemorrhages or clotting of the coil. We conclude that prostacyclin can safely replace heparin as the sole antithrombotic agent during hemodialysis and may be more advantageous if anticoagulation is contraindicated.