Three cornerstones of mast cell development are an absolute dependence on the presence of stem cell factor, T-cell-independent and T-cell-dependent tissue mast cell populations derived from a single lineage, and a diversity of phenotypes for mature tissue mast cells as defined by immunohistochemical and biochemical properties. The in vivo biology of the mast cell in the mouse has been deduced through the availability of mice with genetic and induced gene disruptions, whereas limited but compatible findings for the human have been acquired through the study of patients with systemic mastocytosis and T-cell deficiency. The characteristics of mast cells recognized from these in situ circumstances can be used to establish culture systems for obtaining mouse and human mast cells from progenitor cell sources. These cells allow studies of receptor-mediated gene regulation by cytokines derived from both stromal cells and T cells.