In a randomized double-blind trial, patients with ischemic rest pain of the leg received 8 days of treatment with intravenous injections of the defibrinating agent, ancrod (Arvin) or saline. Plasma fibrinogen, plasma viscosity, and blood viscosity were significantly reduced during ancrod therapy. After 27 patients had completed treatment, sequential analysis showed no preference for either therapy. In each group two-thirds of the patients claimed improvement in pain after treatment. There were no significant differences between treatment groups in analgesic consumption, Doppler systolic pressure ratio, or surgical intervention in the 6 months following treatment. We conclude that in patients with ischemic rest pain, ancrod therapy is not superior to placebo injections, and that the effect of placebo treatment is considerable.