The purpose of this study was to evaluate the differences between tissue plasminogen activator (TPA) and urokinase (UK) in the management of ischemic limbs. A total of 58 limbs (24 in the TPA group and 34 in the UK group) in 53 patients were studied prospectively. The two groups were based on the surgeon's preference for lytic agent. The dose regimen for UK was 150,000 IU/hr over 1/2 to 2 hr followed by a continuous infusion of 50,000 IU/hr. TPA was given as a 5-mg bolus followed by 1 mg/hr. Both groups received heparin at a rate of 400 IU/hr through the side arm of the arterial sheath. There was no significant difference in efficacy between UK and TPA, but TPA acted faster and had a higher incidence of bleeding complications.