Abstract We have investigated the component in the serum of two patients with dermographia that sensitized normal skin for a wheal-flare response to scratching. Passively sensitized skin sites were more reactive six to eight hours than 1 hour after injection and sometimes remained sensitized for 10 days. Serum activity was destroyed by heating or by reducing and alkylating. After fractionating serum proteins in several ways, activity paralleled concentrations of immunoglobulins E(IgE) and D(IgD), but not of other immunoglobulins. Treatment of serums with an insoluble immunoadsorbent composed of a rabbit antibody preparation to human IgE removed the activity, which was present in protein eluted from the immunoadsorbent. Skin sensitization was prevented by mixing active serums with E myeloma protein or with normal IgE in serum. Skin sites that had become refractory to IgE-mediated reactions could not be sensitized. Rabbit and guinea pig skin could not be sensitized by active serum for passive cutaneous anaphylaxis-like reactions to scratching, but a serum fraction rich in IgE did sensitize monkey skin for bluing reactions to scratching three and 24 hours after injection. These results indicate that IgE is responsible for the passive transfer of dermographia to normal human skin by serum from some patients. They further suggest that skin fixation of such dermographia-mediating IgE to tissue mast cells is required for its action.