Transmission electron microscopy was used to characterize early pulmonary lesions in goats after a 2-hour intravenous infusion of 0.04 g 3-methylindole (3MI) per kilogram body weight. Groups of 2 or 3 goats were euthanized at 0.5, 2, 4, 8, and 24 hours after the beginning of the infusion. Changes in lung ultrastructure were compared to noninfused and carrier-infused (propylene glycol) controls. By 0.5 hour, mitochondria and intracellular vesicles were swollen in capillary endothelial, alveolar, and nonciliated bronchiolar epithelial cells. Morphologic changes were most severe in the alveolar Type 1 and nonciliated bronchiolar epithelial cells. Interalveolar septums were swollen at 0.5 hour, and interstitial edema was severe at 2 hours. Denuded alveolar epithelial basement membranes were also observed at 2 hours, and some endothelial cells appeared dark and necrotic. Endothelial cells appeared normal after 2 hours. By 4 hours, the remaining intact alveolar Type 1 cells contained larger and more prominent clusters of smooth endoplasmic reticulum, compared with controls. Morphologic changes in alveolar Type 1 and nonciliated bronchiolar epithelial cells became progressively more severe during the 24-hour experiment. These findings demonstrate that 3MI induces a rapid cytotoxic effect primarily on alveolar Type 1 and nonciliated bronchiolar epithelial cells. Proliferation of smooth endoplasmic reticulum in these cells suggests involvement of the mixed function oxidase system in 3MI-induced pneumotoxicity.