To investigate the modulated proliferation of an interleukin-3(IL-3)-dependent cell by exogenous ganglioside GM3, mouse bone marrow-derived mast cells (BMMC) were cultured with various concentrations of GM3 in the presence of IL-3. By 4 weeks of culture, most of the nonadherent cells were alcian blue-positive mast cells. Culturing 2-week-cultured BMMC with GM3 for 1 week reduced the number of alcian blue-positive cells, but the increased total histamine content of BMMC was observed. To examine the effect of GM3 on the synergistic response by IL-3 and interleukin-4 (IL-4), 3-week-cultured BMMC were cultured with GM3 in the presence of IL-3 and IL-4 for 1 week. Although the addition of IL-4 to culture medium increased the number of BMMC, treatment with GM3 reduced its proliferative activity. Concerning the effect of GM3 on cell membrane, there are no changes in the expression of IgE receptors on BMMC treated with GM3 though a low concentration of GM3 increased it. However, the production of tumor necrosis factor-alpha from BMMC treated with GM3 was significantly suppressed. These results indicate that in vitro treatment with exogenous GM3 inhibited the proliferative response of IL-3-dependent mast cell populations and modulated its characteristics.