A myriad of investigations have been published on the pharmacologic manipulation of flaps to enhance tolerance to ischemia. We recently reported a threefold increase in ischemic tolerance of the rat abdominal skin flap pedicle after 6 hours of primary ischemia and 12 hours of reperfusion. Flaps underwent normothermic perfusion washout with lactated Ringer's or U.W. solution, a newly developed organ preservation medium. Perfusion washouts were performed at one of three different points in the protocol: (1) onset of primary ischemia; (2) onset of secondary ischemia; or (3) 2 hours after onset of secondary ischemia. The last group was used to simulate the clinical situation in which flaps are discovered and salvage procedures instituted at a delayed time interval. This is the longest normothermic ischemic interval reported. We undertook the present study to determine the utility of the U.W solution in prolonging the tolerance of the flap to a second ischemic insult after a period of reperfusion. Seventy-five unilateral rat abdominal skin flaps were raised. Secondary ischemia was produced by placing a microvascular clamp across the inferior epigastric pedicle. Flap survival was assessed at 1 week postoperatively. While none of the nonperfused flaps survived 8 hours of secondary ischemia, at least 50% of the U.W. perfused flaps survived an average of 14 hours of secondary ischemia. Lactated Ringer's perfusion washout only modestly increased the ischemic tolerance. Perfusion washout in the secondary ischemic phase improved the ischemic tolerance to a significantly greater degree than in the primary ischemic interval.