Cardiopulmonary bypass, a form of extracorporeal circulation, markedly increases blood fibrinolytic activity. Accordingly, we measured the effect of hemodialysis, another form of extracorporeal circulation, on fibrinolytic activity in 13 patients with end stage renal disease during and after a single hemodialysis session. Total fibrinolytic activity on fibrin plates, which reflects plasminogen activator levels, was below normal prior to dialysis, rose well above normal at one hour, and then dropped gradually so that just prior to the end of a dialysis session it was still significantly elevated. Within 30 minutes of the end of dialysis, fibrinolytic activity fell rapidly, approaching predialysis levels. In contrast, 5 patients studied before and 3 hours into a peritoneal dialysis session showed no change in their subnormal levels of plasminogen activator. Plasminogen and alpha-2 antiplasmin levels did not change significantly during the course of hemodialysis. Thus, hemodialysis, but not peritoneal dialysis, transiently increases fibrinolytic activity without consuming plasminogen, a pattern consistent with the release of tissue type plasminogen activator.