The proximal renal tubular cells' vulnerability to the direct toxic action of chemicals is largely due to the role played by this nephron portion in absorption and secretion. This is an energy-demanding function so that these cells must have a high rate of oxidative metabolism and thus contain many mitochondria supplying the Na+/K+ pumps at the basolateral plasma membrane domain, thereby driving the carrier systems for entry of water and solutes across the luminal membrane. Thus toxic mechanisms leading directly or indirectly to disturbances of the renal cells' energy metabolism will result in cell injury and acute renal insufficiency. Quantitative morphological-stereological-analysis of at least two, the mercuric chloride- and the maleate-induced experimental models of toxic acute renal failure, show a very early substantial loss of ATP-generating mitochondrial inner membrane surface as well as substantial decrease in those functions protecting cells against oxidative or auto-oxidative processes, i.e. glutathione content, activities of the free-radical-scavenging systems superoxide dismutase, glutathione peroxidase and glutathione reductase and catalase. The cellular dysfunction following these early events may be considered as causative of the subsequent development of most of the morphological alterations described, which are fairly similar in appearance regardless of the toxic principle acting upon the kidney.