Hypothyroidism is associated with changes in renal function and a decrease in kidney weight. The present study was carried out for examination of the effect of the antithyroid drug aminotriazole (ATZ) on kidney structure and especially for determination of whether hypothyroidism affects the whole nephron or only a specific segment of it. Female Sprague-Dawley rats received ATZ in their diet, 0.5 g/kg food for 4 weeks. Control rats received a normal diet. Additional groups of animals receiving ATZ in the diet were given daily injections of L-thyroxine (T4) for determination of whether ATZ-induced changes could be prevented by thyroid hormone. After collection of physiologic data the kidneys were fixed by in vivo perfusion with 3% glutaraldehyde in preparation for light-microscopic morphometry. Following ATZ treatment there was a significant decrease in serum triiodothyronine (T3) and in GFR. Kidney weights were decreased, mainly because of a reduction of cortical tissue. Morphometry showed no changes in the relative volumes of the various compartments of the kidney, indicating that the decrease in weight involved all segments of the nephron. Direct measurements of tubular diameters revealed a decrease in the peritubular diameters in both proximal tubules and the thick ascending limb and a decreased cell height in the thick ascending limb. All the ATZ-induced changes could be prevented by simultaneous treatment with T4, suggesting that the changes were caused by the antithyroid effect of ATZ and were not a nonspecific toxic effect.