The clinical syndrome of anaphylactic shock is a disorder produced by multiple mechanisms and pharmacological and environmental factors. The syndrome may be produced by both immunologic and nonimmunologic mechanisms and is due to the release of preformed biologically active mediators and the generation of biologically active mediators. The main mediator appears to be histamine. Although there are a number of defined predisposing factors, the majority of first reactions appear unpredictably. The mainstay of treatment is the use of epinephrine, volume replacement, and positive pressure ventilation. The follow-up and documentation of details of the reaction and exhaustive efforts to determine the precipitating factor are important aspects of the subsequent safety of the patient. History may be of more value than diagnostic testing. The use of H1 and H2 blockers, with steroids and sympathomimetics, may reduce the risk or magnitude of reactions in patients with a past history of a reaction.