The effects of ATP-MgCl2 and dipyridamole were evaluated in a canine model. Twenty-five adult mongrel dogs were divided into five equal groups. All dogs underwent left nephrectomy and 30 min of warm ischemia followed by Collins' C-4 flush and 24 hr of cold-storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy were then performed. Group A served as controls; Group B was pretreated with intravenous ATP-MgCl2 (2.5 mM); Group C with intravenous dipyridamole (10 mg), and Group D with both ATP-MgCl2 (2.5 mM) and dipyridamole (10 mg). Group E was treated with ATP-MgCl2 (2.5 mM) at the time of transplantation. All kidneys underwent cortical biopsies at the end of preservation and 1 hr after restoration of blood flow for determinations of AMP, ADP, and ATP. In Groups A and E there were no survivors, whereas Groups B, C, and D had 40, 60, and 40% graft survival. In Groups B and D, ATP and energy charge (EC) were greater than that of controls after 24 hr of preservation, with Group D values being significantly greater (P less than 0.01). AMP and ADP levels were significantly greater (P less than 0.02) in Group C when compared to Group A. One hour posttransplantation biopsies demonstrated greater ability to regenerate cortical nucleotides in the surviving animals, but no absolute value could be identified as a predictor of viability. In conclusion, pretreatment with ATP-MgCl2 or dipyridamole maintains intracellular nucleotide levels and has a beneficial effect on graft survival in ischemically injured kidneys undergoing cold-storage preservation.