N-(3,5-Dichlorophenyl)succinimide (NDPS) is an experimental fungicide which induces renal toxicity. The following study examined the nephrotoxicity induced by NDPS in streptozotocin (STZ) diabetic rats. Male Fischer 344 (F344) rats were injected with 35 mg/kg STZ (i.p.) or citrate buffer. Fourteen days after STZ or citrate buffer injection, the rats (4-6 rats/group) were injected with (0.4 or 1.0 mmol/kg) NDPS or vehicle (sesame oil, 2.5 ml/kg). Kidney weight, blood urea nitrogen (BUN) levels, morphology and renal cortical slice uptake of organic ions was quantitated 48 h after NDPS administration. A 0.4 mmol/kg dose of NDPS induced diuresis, increased kidney weight and a moderate elevation in BUN levels in the normoglycemic group. The 1.0 mmol/kg dose of NDPS produced diuresis, proteinuria, increased kidney weight and a marked increase in BUN levels in the normoglycemic group. The renal cortical slice uptake of p-aminohippurate (PAH) and tetraethylammonium (TEA) was also decreased 48 h after NDPS injection in the normoglycemic group. No alterations in kidney weight, BUN levels, morphology or renal cortical slice uptake of organic ions was observed in the diabetic animals treated with (0.4 or 1.0 mmol/kg) NDPS. The results of this study indicate that the renal toxicity of NDPS was reduced in the diabetic rat.