Oxygen-free radicals have been implicated as mediators of ischemic damage in a number of tissues, including heart, kidney, small intestine, and skin. Superoxide dismutase, a free radical scavenger, and allopurinol, an inhibitor of xanthine oxidase (a catalyst in the formation of superoxide) have been shown separately to decrease ischemic damage to tissue. Sixty-two male Sprague-Dawley rats (220 to 280 g) were divided into five groups: control, superoxide dismutase only, allopurinol only, high-dose combined allopurinol and superoxide dismutase, and low-dose combined allopurinol and superoxide dismutase. An 18-cm2 ventral island skin flap, based on a single inferior epigastric vessel, was raised and replaced. Blood flow was assessed with a perfusion fluorometer immediately after the flap was replaced, and on postoperative days 1 and 3. Gross necrosis was assessed on postoperative day 7. Gross necrosis was reliably reduced in all groups as compared with the control; however, necrosis in any one experimental group was not significantly different from any other experimental group. Necrosis (expressed as a percentage of the area of the random [distal] half of the flap) was as follows for each group: control, 74%; superoxide dismutase, 43%; allopurinol, 43%; high-dose combined, 48%; low-dose combined, 33%. Blood flow, as represented by the dermofluorescence index, was not changed by any of the treatments. Blood flow was also related to the eventual survival or necrosis for any one portion of tissue. All experimental groups survived with significantly less blood flow than the control.(ABSTRACT TRUNCATED AT 250 WORDS)