Renal cortical microsomal vesicles possess an ATP-dependent Ca 2+ uptake system which is two to three times more active in accumulating Ca 2+ than are the microsomes prepared from the outer medulla or papilla of the cat kidney. The microsomal Ca 2+ uptake system was unaffected by sodium azide, and electron microscopy confirmed the absence of intact mitochondria. Ca 2+ accumulating activity was significantly increased by 13 per cent in cortical microsomes prepared from kidneys which had been perfused with isoproterenol (2 × 10 −7 M), whereas medullary or papillary microsomal Ca 2+ accumulation was unaffected. Perfusate containing a higher isoproterenol concentration (2 × 10 −6 M) stimulated cortical as well as papillary microsomal Ca 2+ uptake by 13 and 31 per cent respectively, but had no effect on medullary microsomal Ca 2+ accumulation. A lower isoproterenol concentration (2 × 10 −8 M) did not change the Ca 2+ uptake activity of microsomes isolated from either region of the cat kidney. The isoproterenol concentrations (2 × 10 −7 and 2 × 10 −6 M) which activated Ca 2+ uptake in microsomes produced graded increases in renin secretion, whereas 2 × 10 −8 M isoproterenol was relatively inactive in eliciting renin secretion. Renal cortical tissue exposed to cyclic AMP (cAMP) and 5'-AMP during subcellular fractionation showed significant increases in microsomal Ca 2+ uptake. However, microsomes exposed to cAMP or 5'-AMP in the Ca 2+ uptake medium were not stimulated. Isoproterenol also activated Ca 2+ uptake by microsomes prepared from isolated glomeruli, and this stimulation was blocked by propranolol. We conclude that the cat renal cortex possesses specific receptors for isoproterenol which activate Ca 2+ transport through a nucleotide mediated mechanism.