We know that an urticarial wheal can be produced in normal persons by the injection of histamine, morphine and innumerable other substances and also by localized mechanical, thermal or electrical injury. We also know that in patients with serum sickness, hay fever, asthma, and eczema the intradermal injection of the substances to which they are sensitized produces a wheal although these substances have no such effect on normal skin. The serum of allergic subjects will often locally sensitize the skin of normal persons so that it in turn will react to subsequent injection of the allergen or, in some instances, to absorption of the allergen after it is swallowed. The investigations of Philippson, Lewis, Blackley, Prausnitz and Küstner, Walzer and others have established these facts and added greatly to our knowledge of the pathogenesis of wheals. There remains, however, a gap between our understanding of the mechanism of wheal formation