Fructose-1,6-diphosphate (FDP) improves survival in experimental shock. To determine if FDP would protect against single organ damage, rats pretreated with an intravenous infusion of 5% FDP were subjected to 30 minutes of bilateral renal artery occlusion. Controls received an equal volume of a dextrose and sodium chloride solution. Renal function and histology were examined in all groups 24 hours after the insult. Following ischemia, FDP-treated rats had inulin clearances (FDP 897 +/- 129 vs control 349 +/- 59 microliter/min/100 gm BW; P less than 0.01) and solute excretion rates (FDP 6,386 +/- 1,346 vs control 2,602 +/- 396 mOsm/kg/min/100 gm BW; P less than 0.05) greater than control and not different (P-NS) from sham-operated rats. Renal histology was better preserved in the FDP-pretreated group. Thus, pretreatment with FDP provides histologic and functional protection from an ischemic renal insult.