Response to 3-methylindole (3MI) varies among species. Mice recover from 3MI-induced bronchiolar epithelial injury but sustain persistent olfactory mucosal injury with scarring and epithelial metaplasia. In contrast, 3MI induces obliterative bronchiolitis in horses and ponies, but olfactory mucosal injury has not been reported. To evaluate the effect of 3MI on equine olfactory mucosa, ponies were dosed orally with 100 mg 3MI/kg (n = 9) or corn oil vehicle (n = 6). All ponies treated with 3MI developed obliterative bronchiolitis with mild olfactory injury. By 3 days after 3MI dosing, olfactory epithelium appeared disorganized with decreased and uneven surface height and scalloping of the basement membrane zone. Epithelial cells of Bowman's glands were hypertrophic. Proliferation of olfactory epithelium and Bowman's glands was supported by an increased mitotic index and positive immunohistochemical staining for proliferating cell nuclear antigen as compared with controls. The activity of 11beta-hydroxysteroid dehydrogenase, an olfactory mucosal cytosolic enzyme localized to sustentacular and Bowman's glandular epithelial cells, was concurrently decreased. By 9 days postdosing, olfactory mucosal lesions had lessened. Results indicate that 3MI transiently injures equine olfactory mucosa without the extensive necrosis, scarring, or metaplasia seen in murine olfactory mucosa or in equine bronchiolar epithelium.