This study was designed to assess effects of carbon tetrachloride (CCl4) in hamster tracheal epithelium. Adult, male, Syrian golden hamsters were treated with 2.5 ml/kg CCl4 ip, and controls received only the vehicle (peanut oil). Animals were sacrificed after 1, 4, 12, and 24 h. Tissue samples from upper and lower tracheal levels were fixed and embedded in glycol methacrylate for light microscopy. Some tracheal rings were also fixed in formaldehyde/glutaraldehyde cacodylate buffer for transmission electron microscopy. For histopathologic evaluation of the tracheal epithelial cells, each tracheal level was cut transversely at 3 microns and stained with toluidine blue. CCl4 produced injury to ciliated and nonciliated cells in all portions of hamster trachea, although the severity of CCl4-induced injury differed in various levels and regions. The number of damaged cells increased markedly after 1 h in the lower trachea, but not until after 4 h in the upper trachea. By 24 h, the number of injured cells had decreased so that no significant difference from control was evident. The ultrastructural alterations in epithelial cells were obvious as early as 1 h after CCl4 administration. Intracellular organelles, including smooth and rough endoplasmic reticulum, mitochondria, and Golgi apparatuses, were damaged by this chemical. Since CCl4-induced cell injury is dependent on metabolism by intracellular NADPH-dependent cytochrome P450 monooxygenases, these results suggest that hamster tracheal epithelial cells have the potential to activate CCl4 metabolically.