The activation of mast cells (MC) due to immunological stimulation causes an immediate and dramatic inflammatory response. We review current evidence indicating that the membrane permeabilities for calcium, chloride, sodium, and potassium have a significant role in the activation of these cells, and in some cases, specific ionic channels have been identified. Moreover, a number of intracellular mechanisms controlling these channels are pointed out, including different classes of G proteins, intracellular calcium, cAMP, and products of phosphoinositol breakdown. However, the interplay between factors controlling membrane conductances for different ions is not currently understood. The diversity of ionic effects on MC activation is depicted, illustrating that the ionic mechanisms of MC activation are specific for different MC types. Since nerve/mast cell interaction is a key element in the burgeoning field of neuroimmunology, we discuss the role of ionic channels as targets of neurotransmitter action in MC activation.Key words: ionic channels, mast cells, neuroimmunology.