The purpose of this study was to determine whether corneal epithelial defects and epitheliopathy in patients with unilateral dysfunction of the ophthalmic division of the trigeminal nerve (neurotrophic keratitis) is associated with reduced aqueous tear production. Sensation of the skin, cornea, and nasal mucosa, aqueous tear production by Schirmer 1 testing, nasal-lacrimal reflex, and exposure zone rose bengal staining were evaluated in the affected and fellow eyes of subjects with neurotrophic keratitis (n = 5), eyes of subjects who had recent herpes zoster ophthalmicus (HZO) and who did not develop neurotrophic keratitis (n = 4), and normal controls (n = 10). Sensation in the brow and upper lid skin and nasal mucosa was absent on the affected side of patients with neurotrophic keratitis, but was intact in all other groups. Corneal sensation and Schirmer 1 test values were significantly reduced (p < or = 0.05) in eyes with neurotrophic keratitis compared with the other groups. The nasal-lacrimal reflex was absent on the involved side of subjects with neurotrophic keratitis but was intact in subjects with HZO without keratopathy, and in normal controls (p < 0.008). Rose bengal keratitis staining scores were significantly increased in eyes with neurotrophic keratitis compared with the other groups (p < 0.05). We conclude that neurotrophic keratitis is associated with reduced cutaneous, nasal mucosal, and corneal sensation on the affected side, as well as marked reduction in aqueous tear production with loss of the nasal-lacrimal reflex. It is possible that the corneal epithelial pathology in neurotrophic keratitis is due in part to aqueous tear deficiency.