The growth and differentiation in vitro of rodent mast cells, a process dependent upon interleukin (IL)-3, has already been well established. Only recently, however, have the mechanisms underlying the development in vitro of human metachromatic cells (basophils and mast cells) begun to be delineated. Precursors of human metachromatic cells are found in bone marrow, peripheral blood, cord blood, fetal liver and are represented by some leukemic cell lines. These are dependent upon the presence of several cytokines or accessory cells for their proper growth and differentiation. IL-3 as well as granulocyte-macrophage/colony-stimulating factor (GM-CSF) appear to be the principal human metachromatic cell hemopoietic factors; contributory roles to metachromatic cell differentiation can also be shown for IL-5 and nerve growth factor. Stromal cell populations, including fibroblasts and epithelial cells, especially from allergic or inflamed tissue microenvironments, elaborate GM-CSF and possibly novel metachromatic cell differentiation factors. Questions remain regarding cell origins, specific hemopoietic factors and lineage inter-relationships for human mast cell subtypes and basophils. The intriguing possibility of mast cell-drived hemopoietic cytokines, which could perpetuate human allergic reactions, is currently under scrutiny. The relevance of existing data and future research in this area to diagnosis and therapy of a large group of human immune-inflammatory conditions is not to be underestimated.