Various biochemical parameters of renal tubular function were examined for a period of up to 12 weeks in rats rendered diabetic by an i.v. injection of streptozotocin. Except for a statistically significant decrease in the urinary excretion ofγ-glutamyl-transpeptidase to 64% of control values, the urinary excretion ofβ-N-acetyl-D-glucosaminidase,β-galactosidase, alanine aminopeptidase, and lactate dehydrogenase significantly increases in diabetic rats to betwen 154% and 712% of control values. This increased enzymuria is not correlated to the marked polyuria induced by diabetes (r between 0.14 and 0.35, not significant). Enzymuria is also accompanied by a 10-fold increase in the urinary excretion of the low molecular weight proteinβ2-microglobulin while the excretion of albumin is not significantly modified, indicating impairment of tubular reabsorption in diabetic animals. Clearance studies reveal that the clearance of bothβ2-microglobulin and infused egg-white lysozyme are also increased. Finally the histopathologic examination of paraffin sections of the kidney show hydropic degenerescence and pycnosis of the tubular cells. It is concluded that early-stage diabetes results in tubular impairment and that the streptozotocin-rat model appears well suited to the study of these early signs of renal dysfunction.