Anaphylaxis was first described in 1902 by Portier and Richet1 as “against, or without, protection” in contrast to prophylaxis, which implies protection from disease. Today, we distinguish anaphylaxis, a type I, IgE-mediated, immediate response to a foreign substance (such as a drug—penicillin or other foreign protein—horse serum) from anaphylactoid reactions (such as is seen after contrast media), which are similar in presentation to anaphylaxis but do not involve IgE. Anaphylactic reactions are prototypical allergic reactions that represent an extreme example of type I hypersensitivity. We can usually differentiate substances that cause anaphylaxis (penicillin or peanut allergy) from other substances that cause allergic reactions in the nose (allergic rhinitis caused by ragweed pollen or cat dander) or in the lungs (extrinsic asthma provoked by dust mites). Obviously, systemically administered agents are more likely to cause anaphylaxis, whereas aeroallergens most often trigger rhinitis and asthma. Thus ragweed extract may cause anaphylaxis when given as immunotherapy and rhinitis may occur in a worker exposed to aerosolized penicillin. Moreover, with sufficient exposure during the height of the ragweed pollen season some patients may have systemic manifestations of allergy such as urticaria, which may represent mild anaphylaxis. Consequently, it may not always be easy to differentiate anaphylaxis from other allergic disorders. It may also not be easy to differentiate anaphylactic from anaphylactoid reactions. What then is idiopathic anaphylaxis? Idiopathic anaphylaxis is a relatively new diagnosis 2 and represents an anaphylactic reaction without a recognizable cause or an anaphylactoid reaction without either a recognized cause or mechanism. Surely idiopathic anaphylaxis is a perplexing condition for physicians, especially primary care providers, who should refer those patients who do not have an obvious trigger for evaluation by a specialist. In its extreme form, anaphylaxis may cause abnormalities of the airways (upper and lower), cardiovascular system, gastrointestinal system, and skin manifested by laryngeal edema, stridor, and airway compromise; hypotension, vascular collapse, and cardiac arrest; severe abdominal cramping with vomiting; and angioedema. Such an attack of anaphylactic shock would generally demand immediate attention (without time for an “allergy” consultation). Proper treatment would depend on a proper diagnosis, which is typically based only on a well-taken, albeit rapid, history and a focused physical examination without any laboratory testing; tests such as the measurement of histamine or tryptase only serve to confirm a diagnosis, long after the attack has ended. Less severe cases of anaphylaxis might be more difficult to diagnose, and in its mildest forms anaphylaxis may be indistinguishable from allergy (of the skin, nose, or lungs). Indeed, in some settings, such as in the operating room, anaphylaxis may be missed altogether because the patient cannot complain of pruritus, a metallic taste, or the feeling of impending doom, all of which are so characteristic of anaphylaxis. We think that anaphylaxis in the operating room is relatively common, 3 especially since the advent of the current epidemic of latex allergy, 4 although some past studies have shown anaphylaxis to be relatively uncommon in the operating room.5