Tetraethyl orthosilicate (Si(OC2H5)4, or TEOS) is a silicon-containing compound which has widespread industrial applications and which has been documented as biohazardous. The histopathological features and mechanism of TEOS toxicity in the kidney of ICR mice were investigated in a light and electron microscopy study, which included energy dispersive X-ray microanalysis. TEOS was given to mice as intraperitoneal injection of approximately 1,670 mg/kg body weight in experiments based on a 24 h time-scale. Tissues were examined after sampling either immediately on death if this occurred within 24 h or, in the case of surviving animals, after sacrifice at 24 h. Renal injury was considered to be the most probable cause of death, on the basis of the following main findings: 1) acute tubular necrosis (glomerular lesions were absent); 2) a dense deposit of silicon over the microvilli of dead tubular epithelial cells; 3) an abundant aggregation of hydroxyapatite crystals containing calcium in the cytoplasm and mitochondria of the dead tubular epithelial cells; and 4) abundant myelinosomes and some hydroxyapatite crystals in the cytoplasm of viable proximal convoluted tubule epithelial cells. It was speculated that silicon compounds may bind to the plasma membranes of the proximal convoluted tubule epithelial cell microvilli and damage or interfere with membrane calcium channels. The resulting calcium ion imbalance may play a role in the subsequent progression of acute tubular necrosis by TEOS.