This study investigates the effect in rats of acute CdCl₂(5 μM) intoxication on renal function and characterizes the transport of Ca²⁺, Cd²⁺, and Zn²⁺in the proximal tubule (PT), loop of Henle (LH), and terminal segments of the nephron (DT) using whole kidney clearance and nephron microinjection techniques. Acute Cd²⁺injection resulted in renal losses of Na⁺, K⁺, Ca²⁺, Mg²⁺, PO₄⁻², and water, but the glomerular filtration rate remained stable.⁴⁵Ca microinjections showed that Ca²⁺permeability in the DT was strongly inhibited by Cd²⁺(20 μM), Gd³⁺(100 μM), and La³⁺(1 mM), whereas nifedipine (20 μM) had no effect.¹⁰⁹Cd and⁶⁵Zn²⁺microinjections showed that each segment of nephron was permeable to these metals. In the PT, 95% of injected amounts of¹⁰⁹Cd were taken up.¹⁰⁹Cd fluxes were inhibited by Gd³⁺(90 μM), Co²⁺(100 μM), and Fe²⁺(100 μM) in all nephron segments. Bumetanide (50 μM) only inhibited¹⁰⁹Cd fluxes in LH; Zn²⁺(50 and 500 μM) inhibited transport of¹⁰⁹Cd in DT. In conclusion, these results indicate that 1) the renal effects of acute Cd²⁺intoxication are suggestive of proximal tubulopathy; 2) Cd²⁺inhibits Ca²⁺reabsorption possibly through the epithelial Ca²⁺channel in the DT, and this blockade could account for the hypercalciuria associated with Cd²⁺intoxication; 3) the PT is the major site of Cd²⁺reabsorption; 4) the paracellular pathway and DMT1 could be involved in Cd²⁺reabsorption along the LH; 5) DMT1 may be one of the major transporters of Cd²⁺in the DT; and 6) Zn²⁺is taken up along each part of the nephron and its transport in the terminal segments could occur via DMT1.