Background: Olopatadine, an antihistamine used in allergic conjunctivitis, is under development as a nasal preparation for the treatment of allergic rhinitis. Objectives: To evaluate the efficacy of olopatadine in suppressing symptoms and biomarkers of the immediate reaction induced by nasal allergen provocation and to compare olopatadine with azelastine in the same model. Methods: The study was approved by the Johns Hopkins University institutional review board, and all subjects gave written consent. We studied 20 asymptomatic subjects with seasonal allergic rhinitis. The study had 2 randomized, double-blind, placebo-controlled, crossover phases that evaluated 2 concentrations of olopatadine, 0.1% and 0.2%. In a third exploratory phase, olopatadine, 0.1%, was compared with topical azelastine, 0.1%, in a patient-masked design. Efficacy variables were the allergen-induced sneezes, other clinical symptoms, and the levels of histamine, tryptase, albumin, lysozyme, and cysteinyl-leukotrienes (third study only) in nasal lavage fluids. Results: Both concentrations of olopatadine produced significant inhibition of all nasal symptoms, compared with placebo. Olopatadine, 0.1%, inhibited lysozyme levels, but olopatadine, 0.2%, inhibited histamine, albumin, and lysozyme. The effects of olopatadine, 0.1%, were comparable to those of azelastine, 0.1%. Conclusions: Olopatadine, at 0.1% and 0.2% concentrations, was effective in suppressing allergen-induced nasal symptoms. At 0.2%, olopatadine provided evidence suggestive of inhibition of mast cell degranulation.