A gradual loss of olfactory capability with age and in a number of neurodegenerative diseases is common, and mechanisms underlying these losses are not understood. We determined the feasibility of using ORNs obtained from olfactory epithelial biopsies to identify possible changes in ORN function that may contribute to olfactory impairment in these individuals. ORNs from nine healthy subjects (66-84 yr), three patients with Alzheimer's disease and one with multi-infarct dementia were studied with calcium imaging techniques and two odorant mixtures. Seventy-five viable ORNs were studied; 53% of these were odorant responsive, and twenty percent of these responded to both odorant mixtures. In contrast, 25% of 173 ORNs from younger subjects were odorant responsive, and none of these responded to both odorant mixtures. The proportion of cells responding to each of the odorant mixtures also differed between older and younger subjects. These studies demonstrate the feasibility of this approach to examine age or disease-associated changes in neuronal function. Further, age-related changes in ORN selectivity may contribute to changes in olfactory performance.