Autoantibodies recognizing critical effector molecules of type I allergic reactions have been identified. Anti-IgE autoantibodies occur at high frequencies not only in atopic diseases but also in healthy individuals and, depending on their epitope specificities, may promote or prevent the elicitation of allergic symptoms. In contrast, anti-Fc epsilon RI autoantibodies with basophil/mast cell activating properties were selectively found in patients with chronic urticaria, a condition characterized by the continuous degranulation of mast cells. Thus, humoral anti-Fc epsilon RI autoreactivity defines a distinctive subset of chronic urticaria and may well be the causative and pathogenetic principle in this disease.