Few data are yet available comparing the histological patterns of cadmium nephropathy with the values of urinary enzyme excretions, useful indexes of renal tubular damage. 40 Wistar rats, divided into four groups (A-D), were intoxicated with cadmium chloride (CdCl2) at 16 ppm in drinking water for 4, 16, 40 and 60 weeks, respectively. At the end of each period all the intoxicated rats and 5 controls were assessed for creatinine clearance, fractional excretion of gamma-glutamyltransferase (UfrGGT) and alpha-glucosidase (UfrAGL), indexes of anatomical tubular damage, and for fractional clearance of lysozyme (CfrLys), index of functional tubular damage. Thereafter, the rats were sacrificed and their kidneys examined with light and electron microscopy. Control rats and group A and B rats did not show any histological impairment. A widespread vesiculation of proximal tubular cells with mitochondrial and lysosomal alterations was found in the group C rats and was more evident in group D. The brush border never showed any damage in all groups in accordance with the finding of a normal excretion pattern of UfrGGT, an enzyme situated in this structure. The UfrAGL was increased only in group D rats (p less than 0.025), who showed the most severe anatomical damages. The CfrLys, an index of tubular function, was elevated in group C and D rats (p less than 0.02 and p less than 0.002, respectively). It was possible to detect the initial renal tubular damage.