Basophil granulocytes and tissue mast cells and their mediators play a role in the pathogenesis of several immune and inflammatory disorders. Human basophils and mast cells (FcεRI+ cells) can be activated through immunological interaction with the IgE-FcεRI network. FcεRI+ cells can be triggered by cross-linking between the Fab portions of IgE and multivalent antigens (direct anaphylaxis). ‘Reverse type’ anaphylaxis can occur through three distinct mechanisms: antibodies against the Fcε portion of IgE (anti-IgE), antibodies against epitopes of the α chain of FcεRI (anti-FcεRIα) and anti-IgG acting on IgG–IgE complexes bound to FcεRI. Anti-IgE autoantibodies are occasionally present even in normal donors and more frequently in a variety of allergic (chronic urticaria, atopic dermatitis and bronchial asthma) and autoimmune disorders (rheumatoid arthritis, lupus erythematosus and systemic sclerosis). IgG anti-IgE from a small percentage of patients induces the release of mediators from human FcεRI+ cells. Some of the anti-IgE autoantibodies present in allergic patients are non-anaphylactogenic, thus representing a possible protective mechanism preventing the association of IgE with FcεRI. Anti-FcεRIα autoantibodies also occur in a significant percentage of patients of chronic urticaria and probably non-allergic asthma and some autoimmune diseases. Although anti-IgE and anti-FcεRIα autoantibodies, present in a percentage of patients with immune disorders, are relevant to the pathogenesis of these conditions, much remains to be learnt about their immunochemistry, their prevalence and precise role in various inflammatory diseases.