Abstract Immature, rIL-3-dependent mouse bone marrow-derived mast cells (BMMC) contain high steady-state levels of the mouse mast cell protease (mMCP) 5 transcript but undetectable levels of the mMCP-1, mMCP-2, or mMCP-4 transcripts even though all four of their genes reside at a locus on chromosome 14. These mast cells can be induced by recombinant c-kit ligand (rKL) to obtain high steady-state levels of the mMCP-4 transcript and by rIL-10 to obtain high steady-state levels of the mMCP-1 and mMCP-2 transcripts. rIL-3 and rKL both elicit the differentiation of progenitor cells into immature BMMC and then stimulate their proliferation. We now report that although rIL-9 alone has no effect on BMMC proliferation as assessed by their incorporation of [3H]thymidine, rIL-9 in combination with rKL enhances the long term viability of BMMC. Furthermore, rIL-9 in the presence of rKL stimulates mouse BMMC to undergo a phenotypic change by inducing accumulation of high steady-state levels of the mMCP-1 and mMCP-2 transcripts. In contrast, in BMMC, the presence of rIL-4 suppresses the rIL-9-induced accumulation of the mMCP-1 and mMCP-2 transcripts, the rIL-10-induced accumulation of the mMCP-1 and mMCP-2 transcripts, and the rKL-induced accumulation of the mMCP-4 transcript, but not the rIL-3-induced accumulation of the mMCP-5 transcript. The presence of rIL-3 also suppresses the rIL-9-induced accumulation of the mMCP-1 and mMCP-2 transcripts. Because of their counter-regulatory actions on the steady-state levels of transcripts that encode three late-expressed serine proteases in BALB/cJ mice, rIL-4 and rIL-3 both inhibit the final stages of differentiation and maturation of mast cells. Because rIL-4, unlike rIL-3, is neither an inducer of early-expressed proteases nor alone a proliferative factor for BMMC, the counterregulatory actions of rIL-3 and rIL-4 on differentiation and maturation of these mouse mast cells are independent of their other functions.