Although histamine is the principal mediator of the immediate allergic reaction, other inflammatory mediators as well as neuropeptides also contribute to rhinorrhea and nasal congestion. Within minutes of exposure to allergen, mast cells produce histamine, leukotriene C 4 , and prostaglandin D 2 . A concomitant increase occurs in neuropeptides and bradykinin. In vitro mast cell activation also leads to the release of tumor necrosis factor-α, several interleukins, and granulocyte-macrophage colony—stimulating factor. Because all these various mediators and neuropeptides may play a role in producing rhinorrhea and congestion, antihistamines alone cannot control all of the symptoms of allergic rhinitis. However, the combination of antihistamines with topical corticosteroids can inhibit the generation, release, and activity of most if not all of the mediators potentially involved in the allergic response.