Hemodialysis performed with prostacyclin (5 ng/kg/min) as a substitute for heparin was studied in 10 patients. The subjects were studied during heparin perfusion alone and during heparin perfusion together with prostacyclin. The authors investigated the effect of two heparin regimens (regimen I: 2,000 U/hr and regimen II: 500 U/hr) upon plasma antithrombin level (IU/mL) and activated thromboplastin time (sec). Our findings show: (1) prostacyclin can substitute for heparin anticoagulation in hemodialysis; (2) the concomitant administration of prostacyclin enhances the anticoagulant effect of heparin, based on the measurement of the activated partial thromboplastin time; (3) the antithrombin activity is increased by both treatments but more so with prostacyclin; and (4) platelet activation plays a role in limiting heparin anticoagulation, a conclusion partly supported by the finding that activated partial thromboplastin time is somewhat more prolonged by heparin when measured in platelet-poor rather than in platelet-rich plasma in the presence of prostacyclin. Physiopathologic implications of these preliminary findings are discussed.