Mast cells (MC)l are widely distributed throughout vascularized tissues and certain epithelia. They represent a source ofpotent mediators ofinflammation (reviewed in references 1-4). These mediators are released after sensitization with IgE immunoglobulins, which are bound to IgE receptors (FceRI) on the MC, and crosslinking with specific multivalent antigen (4). Such activation causes MC to degranulate releasing histamine, heparin, and other sulphated proteoglycans and certain neutral proteases. Activated MC also elaborate newly synthesized mediators such as products of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism (reviewed in references 2-4). MC are widely regarded as critical effector cells in the inflammatory reactions underlying disorders of IgE-dependent immediate hypersensitivity and in the expression ofprotective immunity involving IgE (reviewed in references 1-4).Studies in mice indicate that MC are derived from multipotential bone marrowderived hematopoietic precursors which complete their program of differentiation and maturation in vascularized tissues, epithelia, and serosal cavities (reviewed in references 1, 5). This process results in the generation ofmast cell populations which vary in multiple aspects of their phenotype, including morphology, mediator content, and sensitivity to regulation by cytokines affecting proliferation and maturation (reviewed in reference 1). One such population, referred to as "mucosal" mast cells (MMC) because they occur in the mucosal layer of gastrointestinal tissues, appears to be exquisitely sensitive to regulation by the T cell-associated cytokines IL-3 and IL-4 (1). IL-3 probably represents the major cytokine regulating proliferation ofthis subset (6, 7), whereas in vitro studies indicate that IL-4 can act as a costimulant of proliferation (8). Thus, the mouse MMC population is regulated by products I Abbreviations used in this paper: AbMuLV, Abelson murine leukemia virus; Ag, antigen; BMCMC, bone marrow-derived cultured mast cell ; DNP3o-40-HSA 2,4-dinitrophenyl-human serum albumin; FceRI, cell surface receptor for the Fc portion of IgE; GM-CSF, granulocyte/macrophage colony-stimulating factor ; MC, mast cell; MIP, macrophage inflammatory protein; MMC, mucosal mast cell ; PKC, protein kinase C. J. Exp. MED.