Anaphylaxis represents the maximal variant of an immediate-type allergic reaction involving the whole organism with manifestations in different organ systems. IgE-mediated mast cell and basophil activation is the major pathomechanism; however, immune complex and pseudo-allergic reactions also may lead to the same symptomatology. The most common elicitors are drugs, additives, occupational substances, animal venoms, aeroallergens, and contact urticariogens but also physical factors (cold, heat, ultraviolet light, exercise). When no eliciting factors can be detected, the term "idiopathic anaphylaxis" is used. The diagnosis of idiopathic anaphylaxis is, therefore, a diagnosis of exclusion and may be made only after careful allergy history taking and diagnosis involving in vitro tests. Possible mechanisms underlying the pathophysiology of idiopathic anaphylaxis include undetected diseases (eg, mastocytosis occulta), concomitant anaphylaxis-enhancing medication (b-blockers), secretion of histamine-releasing factor from T lymphocytes, autoantibodies against IgE or IgE receptors, and angiotensin II deficiency. One of the many differential diagnoses of anaphylaxis may have been overlooked. The treatment of idiopathic anaphylaxis follows the rules of antianaphylactic therapy.