This study was undertaken to test the hypothesis that ischemia prior to transplantation causes tubular damage without clinical evidence of graft dysfunction. The urinary excretion of fructose-1,6-bisphosphatase (EC 184.108.40.206, FBPase), a cytosolic enzyme located exclusively in the proximal tubules, and the lysosomal enzyme N-acetyl-β- D -glucosaminidase (EC 220.127.116.11) were measured daily between postoperative days 1 and 4 in 25 renal cadaveric graft recipients who enjoyed an entirely uncomplicated first postoperative month. During the first 4 posttransplant days urinary FBPase excretion was 0.9 ± 0.5 U/g(0.1 ± 0.06 U/mmol) urinary creatinine [ ± SD; range 0.2-2.1 U/g (0.02-0.24 U/mmol)]. Cold ischemia time was 20.6 ± 8.4 h (median 22 h, range: 3-32 h). Multiple regression revealed a significant correlation between cold ischemia time and posttransplant urinary FBPase excretion (multiple R = 0.65, p < 0.001). There were no confounding effects of recipient’s age and gender, number of previous transplants, cyclosporin A levels, warm ischemia time, anastomosis time, donor age and gender. Urinary FBPase excretion was significantly lower in grafts stored for a shorter time than the median cold ischemia time of 22 hours (0.69 ± 0.42 U/g, n = 13) as compared to those stored for a longer period of time (1.13 ± 0.56 U/g; n = 12; p = 0.035). These results indicate that graft injuries occur even in the absence of graft dysfunction and that the duration of cold ischemia itself correlates with a degree of tubular cell damage as defined by urinary FBPase excretion.