The activation of mast cells is of pivotal importance in the pathogenesis of allergic conditions. Mast cell activation can provoke rapid increases in microvascular permeability, induce bronchoconstriction after blood flow, stimulate the recruitment and activation of other inflammatory cells, and has come to be associated with the processes of tissue remodeling and fibrosis. Such changes may be mediated by the release of a range of potent mediators of inflammation: preformed in secretory granules, or newly generated, or both. There are major differences in the responsiveness to various stimuli and to pharmacological agents for mast cells from different body compartments. A method is presented here for the purification of mast cells from enzymatically dispersed human tissues. The methods described for the experimental activation of mast cells can be readily adapted to studies with cell lines or mast cells obtained through long-term culture.