Rat kidneys were flushed in situ with selected preservation solutions prior to clamping the renal vessels for 1 hour. Collins and Euro-Collins flushing solutions did not appear to protect the physiologic or morphologic status of rat kidneys when examined 2 days after the ischemic insult. These experimental groups exhibited serum creatinine levels similar to those seen in ischemic controls, correspondingly low urine creatinine levels, anuria, and significant deterioration of the uriniferous tubules as revealed by light and electron microscopy. In situ flushing with hypertonic Sacks or isotonic phosphate-buffered sucrose solutions, however, resulted in significant improvements in serum and urine creatinine levels, prevented anuria, and dramatically improved the morphologic integrity of the uriniferous tubules. Flushing with a phosphate-buffered sucrose solution that contained ATP-MgCl2 further improved the physiologic and morphologic status of ischemic kidneys to the point that they were indistinguishable from the nonischemic controls. The degree of protection obtained by flushing kidneys with the isotonic phosphate-buffered sucrose solution plus ATP-MgCl2 is greater than that provided by any other single pretreatment or posttreatment for ischemia that is currently available. We, therefore, believe that the use of this procedure can provide a valuable approach to surgical situations in which postischemic acute renal failure is a potential problem.