In this investigation, we describe a modification of Euro-Collins flushing solution which enables this solution to be effective in preventing normothermic postischemic acute renal failure. The left kidneys of Sprague-Dawley rats were briefly flushed in situ by vascular perfusion with Euro-Collins solution and the renal pedicle clamped to render the kidney ischemic and hold the flushing solution in the kidney. Following 1 h of in situ normothermic ischemia, the pedicle clamp was removed and a contralateral nephrectomy of the right kidney performed. In two other groups of rats the same experimental protocol was followed using Euro-Collins solution in which the dextrose in this solution was replaced with a similar osmolal contribution of either sucrose (64 g/l) or mannitol (35 g/l). Rats with kidneys flushed with the standard Euro-Collins solution containing dextrose (n = 24) exhibited significantly higher postischemic daily serum creatinine levels, a greater degree of tubular necrosis, and a higher mortality (75, versus 31%) than unflushed ischemic controls (n = 22). Rats with kidneys flushed with Euro-Collins, containing either sucrose (n = 25) or mannitol (n = 22) in place of dextrose, all survived, exhibited only focal tubular damage as observed by electron microscopy, and most returned to normal serum creatinine levels within 72 h following ischemia. These findings, together with other reports that mannitol- and sucrose-based flushing solutions provide excellent protection during prolonged cold ischemia, strongly argue for the substitution of sucrose, mannitol or other similar protective impermeant agents for dextrose in flushing solutions such as Euro-Collins.