The mast cell granule provides three distinct sources of mediators: (1) preformed and rapidly released (histamine), (2) secondarily formed and generated by the interaction of primary mediators and nearby cells and tissues (leukotrienes), and (3) granule matrix-derived, which are preformed but remain associated with the granule proteoglycans after discharge (proteases) (Table). The granule matrix and its associated mediators may remain in the tissue for hours until removed through degradation, dissolution, or phagocytosis. The events initiated by the mediators depend on the tissues into which they are released. Mediator discharge clearly initiates the events associated with immediate hypersensitivity; however, late-phase reactions occur in response to granule-derived mediators as well. Several manifestations that may result from the introduction of mast cell-derived products within the gastrointestinal tract are shown in Fig. 5. These include increased vascular permeability and secretion of mucus, effects on cell surface receptors, chemotaxis of various cell types, and smooth muscle contraction. Thus the mast cell, because of its unique anatomic location and mediators, may serve both as an initiator of acute inflammation and a propagator of chronic changes as well.