Mast cells participate in reactions of immediate hypersensitivity, and may contribute to a wide variety of other important biological processes as well. Yet it has been difficult to ascertain the precise role of mast cells in many of these reactions. In part, this reflects recognition that different populations of mast cells may vary in mediator content and/or other aspects of phenotype, and therefore may express different functions. Another problem has been the lack of suitable model systems for identifying and quantitating the mast cell's unique roles in biological processes in intact animals. This review will outline the development of promising new approaches for the analysis of mouse mast cell differentiation and phenotypic heterogeneity, and for studying the roles of mast cells in vivo.