In summary, these observations suggest a model for asthma which is summarized in Table III. Initially, mast cells and possibly other bronchial cells, e.g., alveolar macrophages, are activated either in an IgE-dependent or, in intrinsic asthma, in an IgE-independent fashion. These cells release two sets of mediators which may be either preformed or newly synthesized. One set of mediators is responsible for the immediate bronchospastic response. This bronchospasm is transient, readily reversible, and not associated with either airway inflammation or bronchial hyperreactivity. The second set of mediators, however, promote chemotaxis and activation of neutrophils and eosinophils. The subsequent bronchial inflammation causes damage and desquamation of the respiratory epithelium. The increased exposure of irritant receptors results in hyperreactive airways. In addition, these inflammatory cells induce mast cell degranulation and recurrent bronchospasm. Thus, after the initial exposure to allergen, a vicious cycle of inflammation, hyperreactivity and recurrent mast cell degranulation develops, ultimately leading to the pathological picture of chronic asthma.