The survival of mast cells are dependent on two kinds of growth factors, one derived from T cells (IL-3) and another derived from fibroblasts (stem cell factor [SCF]). The 3T3 fibroblast cell line derived from WCB6F(1-)+/+ mouse embryos (+/+ 3T3 fibroblasts) supported the proliferation of bone marrow-derived cultured mast cells (BMCMC) in the PWM-stimulated spleen cell conditioned medium (PWM-SCM), whereas the 3T3 fibroblast cell line from WCB6F1-Sl/Sld mouse embryos (Sl/Sld 3T3 fibroblasts) did not. To study the role of nitric oxide (NO) on the growth of mast cells in BMCMC-fibroblast coculture, we used a NO synthase inhibitor, NG-monomethyl-L-arginine (NGMMA). NGMMA recovered survival and maintained proliferation of mast cells in BMCMC-Sl/Sld 3T3 fibroblasts coculture. Sl/Sld 3T3 fibroblasts as well as 3T3 fibroblasts from NIH(-)+/+, BALB(-)+/+ or Swiss(-)+/+ mouse embryos secreted NO in PWM-SCM, but not in alpha-MEM. SCF protected BMCMC from cytotoxicity of exogenous NO in IL-3-supplemented alpha-MEM. We concluded that SCF might protect BMCMC from cytocidal effect of NO in BMCMC-fibroblasts coculture.