IgE-dependent activation of human mast cells is a central feature of allergy. However, alternative non-IgE-mediated signals derived from the complex inflammatory milieu are also important in driving chronic mast cell activation in many tissues. Irrespective of the point from where pathological secretion is sustained, all mechanisms will change the activity of the final 'effector' ion channels involved in normal stimulus-secretion coupling. IgE-dependent activation of human mast cells is characterised by an influx of extracellular Ca2+, which is essential for subsequent release of both preformed (granule-derived) mediators and newly generated autacoids and cytokines. In addition, flow of ions such as K+ and Cl- are likely to play an important role in mast cell activation through their effect on cell membrane potential and thus Ca2+ influx. Emerging evidence suggests that mast cells express a number of channels carrying K+, Cl- and Ca2+. With current techniques it will be possible to identify the molecular origin of these channels and define precisely their role in mast cell function. Mast cell ion channels offer a novel target for the attenuation of allergic disease.