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The renal response to volume expansion (VE) has been shown to be impaired in streptozotocin (STZ)-induced diabetes. This may contribute to the abnormal maintenance of fluid balance in diabetics. Since calcium channel blockade (CaCb) has been shown to improve renal hemodynamic and tubular functions, the present studies were designed to examine the ability of CaCb to enhance the response of kidneys from diabetic rats to a volume load. Rats were made diabetic by a single injection of STZ (65 mg i.p.), while the control rats received only a vehicle injection. Nisoldipine, a CaCb agent was given to half of the diabetic rats in a dose of 0.015 microgram/kg per min during the acute experiment. The left kidney was denervated in each rat while the right kidney remained innervated. Glomerular filtration rate (GFR) was elevated during VE in all of the rats except in the denervated kidneys of diabetic rats. Nisoldipine improved GFR in most cases. Urine flow increased markedly during VE. This response was enhanced by denervation but depressed in the diabetic rats. Nisoldipine improved the defective volume reflex in primarily the denervated kidneys. Changes in net urinary excretion of water and sodium during VE were significantly lower in the diabetic rats than in the control group. In the nisoldipine treated diabetic rats the VE induced changes in water and sodium excretion returned toward normal in the denervated, but not in the innervated kidneys. The data are consistent with a blunted volume reflex in the diabetic rats that may be improved by CaCb. Impaired sympatho-inhibition in diabetic rats appears to oppose the effects of VE and nisoldipine treatment. CaCb may contribute to the volume reflex by enhanced filtration as well as by reduced tubular reabsorption.