The acute inhalation toxicity of trimethoxysilane was investigated using Sprague-Dawley rats. A series of inhalation exposures was conducted in which five animal/sex were exposed once to trimethoxysilane vapor by static (for 10 or 60 min) or dynamic (for 1 or 4 hr) generation methods and then observed for 14 days postexposure. Under static generation conditions, all animals died during or within 2 hours following exposure to a nearly-saturated vapor concentration of trimethoxysilane for either 10 or 60 min. During the 1-hr static exposure, the analytical concentration of trimethoysilane decreased, over a 22-min period from 60,000 to 3,000 ppm, while the concentration of methanol (a reaction product of trimethoxysilance and water vapor) rose to approximately 111,000 ppm. During the 10-min static exposure, trimethyoxy-silane concentration decreased from 56,000 to 47,000 ppm (methanol concentration increased to 69,000). Clinical signs observed on the day of exposure included central nervous system excitation (e.g., tremors) and respiratory difficulties. During the exposure, a white residue covering the eyes, nose, and mouth was observed. Gross lesions included a mottled red discoloration of the lungs, dark purpose discoloration of the liver, and clear fluid in the traches and thoracic cavity. Microscopic examination of the lungs of rats from the 10-min exposure group included congestion, edema, and fibrin formation. In some rats, there was exfoliation of the bronchiolar epithelial cells.