Anaphylaxis, the most emergent manifestation of allergy, is best described by its clinicopathologic alterations. Sites of involvement include skin (urticaria), upper respiratory tract (laryngeal edema), lower respiratory tract (bronchospasm), and the cardiovascular system (severe hypotension). Ultrastructural analysis of skin biopsy specimens obtained from individuals experiencing exercise-induced anaphylaxis before and immediately after exercise revealed changes indistinguishable from those observed after immunologic challenge of pulmonary mast cells, and included enlargement of the mast cell granules, solubilization (discharge) of mast cell granule contents, and merger of the granule membranes with adjacent granule membranes and the mast cell membranes. Successful reversal of anaphylaxis requires prompt recognition of symptoms and early institution of therapy. Patients prone to exercise-induced anaphylaxis should avoid any foods, drinks, or pharmaceutical agents, particularly acetylsalicylic acid, for 4, and preferably 6, hours before exercise.