OBJECTIVE To determine whether azelastine nasal spray suppresses the dermal response to epicutaneous histamine in allergic patients and the duration of suppression after azelastine use is discontinued. METHODS Seventy-eight patients with seasonal allergic rhinitis were entered into this randomized, double-blind, parallel-group, placebo-controlled study. Patients received either azelastine nasal spray (2 sprays per nostril twice daily) or placebo nasal spray for 14 days. Skin tests were performed 5 hours after the first dose of study drugs to determine the effect of a single dose of azelastine nasal spray on the wheal-and-flare response to histamine. At the end of the 14-day treatment period, skin tests were performed 5 hours after the last dose of study drugs and at 24-hour intervals thereafter, until each patient's wheal-and-flare response to histamine (1.0 and 5.0 mg/mL) returned to within 20% of baseline values. RESULTS A single dose of azelastine nasal spray did not significantly alter the wheal-and-flare response to histamine. The wheal response was within 20% of the baseline value in 82% and 88% (1.0 and 5.0 mg/mL of histamine, respectively) of the patients 5 hours after discontinuing 14 days of treatment with azelastine nasal spray. Wheal responses were within 20% of baseline values 48 hours after treatment was discontinued, whereas flare responses returned to within 20% of baseline within 48 hours in 92% of the patients. CONCLUSIONS Azelastine nasal spray should be discontinued for at least 48 hours before beginning allergy skin test procedures.