Cadmium chloride was administered to Sprague-Dawley rats in drinking water at 100 ppm for 39 weeks. The mean cadmium concentration in kidneys from 5 rats at the end of this period was 102 +/- 17 micrograms g-1 wet weight (mean +/- SE) compared with 0.22 +/- 0.15 microgram g-1 wet weight in a similar group of control rats. Right kidneys were rapidly frozen in propane and small pieces of cortex were prepared for X-ray microanalysis by freeze-substitution in ether/acrolein for 21 days. Analysis of freeze-substituted sections showed that Cd concentrations rose to 3.9 mmol kg-1 of resin embedded tissue (approximately wet weight) in cytoplasm and 6.5 mmol kg-1 in nuclei. At the same time S concentrations rose by 31 percent in nuclei and 23 percent in the cytoplasm. Cd was also present in lysosomes. Cytoplasmic and nuclear ionic (Na, K, Cl, Ca, Mg) concentrations did not change in spite of a considerable decrease in microvillus membrane surface area. The concentration of P also did not change suggesting that nucleoside phosphate levels remained stable. The distribution of Cd and S supports current concepts of cadmium toxicity. Although total kidney Cd was at the critical concentration and extensive damage to microvilli had occurred, there appeared to be no effect on ionic permeability and cell electrolyte balance and, by inference, NaCl reabsorption.