Epidural spinal cord electrical stimulation has been suggested as an alternative treatment in patients with limb-threatening ischemia in whom vascular reconstructive surgery is not possible anymore. We studied the effects of epidural spinal cord electrical stimulation on microcirculatory blood flow in 20 patients with ischemic rest pain and ulcers. Angiography showed occluded crural arteries technically unsuitable for reconstructive surgery. Intravital capillary microscopy was used to assess capillary density and diameter and red blood cell velocity before and after a 1-minute period of arterial occlusion. After epidural spinal cord electrical stimulation 18 patients claimed immediate pain relief, which was confirmed by intravital capillary microscopy. Capillary density increased from 10 to 19/mm2 (p less than 0.001), red blood cell velocity increased from 0.088 to 0.496 mm/sec (p less than 0.001), and peak red blood cell velocity after arterial occlusion increased from 0.092 to 0.548 mm/sec (p less than 0.001). Two patients had no immediate pain relief; they did not show improvement of microcirculatory perfusion, and amputation was necessary. During the follow-up period (3 months to 3 years, mean 27 months), six other patients had recurrent ischemic pain, and amputation was necessary. In 12 patients pain relief continued, and ischemic ulcers healed; capillary microscopy confirmed improved microcirculatory blood flow. Microcirculatory parameters were significantly higher in respondents than in nonrespondents (p less than 0.001). Life-table analysis revealed a cumulative foot salvage of 80% and 56% after 1 and 2 years, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)