The present study was performed to study the participation of histamine H₃ receptors in nasal symptoms using Sch 50971, a potent and selective agonist of the H₃ receptor. Repeated topical application of antigen caused an increase in sneezing and nasal rubbing in sensitized mice. Oral administration of Sch 50971 and imetit, specific H₃-receptor agonists, resulted in an inhibition of nasal symptoms induced by an antigen similar to an H₁-receptor antagonist, cetirizine. Furthermore, simultaneous use of H₃-receptor agonists, Sch 50971 or imetit, and an H₁-receptor antagonist, cetirizine, caused a significant inhibitory effect on nasal symptoms at doses that showed no effect when used separately. The number of eosinophils in the nasal mucosa of mice sensitized with antigen was significantly decreased by cetirizine; however, Sch 50971 and imetit had no effect on eosinophil infiltration. These results clearly indicate that H₃ receptors are involved in the etiology of nasal allergy, and the stimulation of H₃ receptors may be useful as a novel therapeutic approach in nasal allergy.