This article discusses the activation and inhibition of mediator release from skin mast cells. Mast cells are a physiological cell component of the dermal skin with a high density of about 7000 cells/mm and morphological correlation to connective tissue surrounding blood vessels, lymphatic structures, skin appendages and nerves. The development of enzymatic dispersion techniques to isolate mast cells from human skin allows biochemical and pharmacological characterization of skin mast cells in order to identify the exact mechanisms of secretion.