Many agents are capable of mast cell activation (MCA). In the lung, exposure to allergens induces IgE-mediated mast cell degranulation. By this process, chemical mediators are released and attract inflammatory cells that infiltrate the airway wall. This immune response is a potent stimulus for the pathologic changes seen in asthma (e.g., bronchospasm, mucosal edema, airway hyperreactivity, and mucus secretion). One neglected component of the asthmatic response is vascular permeability--the hallmark of mast cell degranulation. Like muscle contraction, vascular permeability occurs rapidly in response to an antigen challenge and is prevented by classic antiasthmatic therapy. Studies with antidromic nerve stimulation have indicated a relationship between MCA and the histamine-induced release of the sensory neuropeptide substance P, which causes vasodilation. Mediators released during the immediate hypersensitivity reaction may attract neutrophils and other chemotactic factors involved in the late allergic response, which includes a recrudescence of MCA caused by the release of histamine-releasing factors. Understanding these pathophysiologic events in asthma will be useful in formulating therapy.