A method has been developed for the enzymic dissociation of rat skin into its component cells. The resulting suspensions contained 3–5% mast cells. The latter were intact as judged by light microscopy and exhibited a low spontaneous release of histamine. Cells obtained from actively sensitized animals released histamine on challenge with specific antigen. The process was rapid, being essentially complete within 1 mm and was both calcium-and temperature-dependent. The cells also responded to antirat IgE and to calcium ionophores but showed a selective, time-dependent reactivity toward defined chemical histamine liberators. On the basis of these results the properties of the cutaneous mast cell are compared with those previously reported for mastocytes from other sources and discussed in terms of the general heterogeneity of this cell population.