Antigen-mediated aggregation of IgE bound to its high-affinity receptor on mast cells or basophils initiates a complex series of biochemical events, resulting in the release of mediators that cause allergic inflammation and anaphylactic reactions. Recent progress has defined the molecular pathways that are involved in stimulating these cells and has shown the importance of protein tyrosine kinases in the subsequent reactions. The activation pathways are regulated both positively and negatively by the interactions of numerous signaling molecules.