Background: Vasomotor rhinitis (VMR) is a hypersensitivity syndrome with heightened reactivity to environmental triggers. Methods: Twenty-two patients with severe VMR were treated nasally with either normal saline or 0.6% olopatadine and challenged nasally with a hyperosmolar mannitol solution. Results: Treatment with 0.6% olopatadine resulted in an improvement in instantaneous nasal symptom scores at 5 and 30 minutes (p < 0.01) compared with baseline and at 30 minutes after hyperosmolar challenge compared with saline-pretreated individuals (p < 0.01). There was also an improvement in nasal peak inspiratory flow rate at 30 minutes after hyperosmolar challenge compared with saline-pretreated individuals (p < 0.01). Conclusion: In this patient population 0.6% olopatadine appears to be efficacious in symptom reduction in VMR and protects from hyperosmolar challenge.