Parosmia, a smelling disorder, is a symptom of allergic rhinitis. In allergic patients, histamine and leukotriene are released from mast cells or basophils and function as inflammatory mediators. Here, we hypothesized that histamine may modify olfactory information and affect the sense of smelling. We measured the histamine response in isolated olfactory receptor cells (ORCs) using a calcium imaging technique. ORCs were isolated enzymatically from amphibian (newt) or mammalian (mouse, rat) olfactory epithelium and were loaded with Fura-2, a fluorescent calcium indicator. Odorants (100μM amyl acetate, acetophenone, limonene, cineole, geraniol and citonellal) are known to increase intracellular calcium concentration in specific ORCs. A bath application of 100μM histamine also increased the intracellular calcium concentration by 28-33% in the ORCs. This result suggests that histamine receptors are expressed in some ORCs. Olfaction is determined by a combination of ORC responses. Since partial ORCs responded to histamine, the odorant response of ORCs may be altered in the presence of histamine. Therefore, we suggest that histamine-induced changes of a combination of ORC responses might be responsible for parosmia in patients with allergic rhinitis.