The effects of the organic calcium antagonist diltiazem (DIL) upon the alterations in renal hemodynamics produced by norepinephrine (NE) were assessed in the isolated perfused rat kidney. In the presence of propranolol, the administration of NE (3 X 10(-7)M) caused sustained reductions in renal perfusate flow (RPF) and glomerular filtration rate (GFR). The administration of 10(-5) M DIL to NE-treated kidneys did not reverse the NE-induced decrease in RPF. In contrast, DIL produced a striking reversal of the NE-induced decrease in GFR. In the absence of NE-treatment, DIL did not alter GFR or RPF. We conclude that NE-induced constriction of major postglomerular resistance vessels of the rat kidney is not inhibited by DIL. In contrast, the DIL-induced increase in GFR of the NE-treated kidneys indicates that the NE-constriction of preglomerular resistance vessels is inhibited by this organic Ca entry blocker. Under identical conditions, manganese, an inorganic calcium entry blocker, reversed the NE-induced reductions in both RPF and GFR, indicating that although both responses depend upon Ca entry, only the latter is sensitive to DIL. These data are, therefore, consistent with the postulate that different regions of the renal vasculature are heterogeneous with regard to the mechanisms mediating NE-induced vasoconstriction.