Rat basophilic leukemia (RBL) cells are considered to be similar to bone-marrow derived mast cells and to mucosal mast cells (MMC), the latter of which may be involved in inflammatory bowel diseases. RBL cells are not able to accumulate histamine and secretory granules under regular growing conditions. Here we show that the flavonoid quercetin, which inhibits mast cell secretion of histamine, also inhibited RBL cell proliferation and constitutive histamine release while it induced synthesis of rat mast cell protease (RMCP) II and triggered processes leading to accumulation of secretory granules. Cell viability was also retained in the presence of quercetin, whereas untreated cells did not survive past 6 days of growth. Quercetin did not affect the expression of mRNA for alpha-subunit of immunoglobulin E (IgE) receptor, but led to increased expression of mRNA for, and synthesis of RMCP II, which is a marker protein for MMC. Many of these granules showed metachromasia with toluidine blue after 3 days of growth, stained red with alcian blue counterstained with safranin after 8 days of growth, and contained electron dense material. Our results suggest that RBL cells have the capacity to progress to a more mature state and may lend themselves to further analysis of a growth regulator(s) with action similar to that of quercetin.