The receptor tyrosine kinase Axl which expresses extracellular domains reminiscent of cell adhesion molecules, is involved in homotypic binding as well as in intracellular signaling of myeloid progenitor cells. In order to investigate factors which might influence differentiation pathways through changes of the adhesive properties of cells, we analyzed the expression of axl in immature basophil and mast cell lines and in cultured basophil and mast cell precursors. Axl expression was induced by interferon-alpha in the human leukemic mast cell line HMC-1 and in cultured mast cells derived from CD34+ peripheral blood cells. Axl induction was dose dependent, appeared within 1 h, and was independent of de novo protein synthesis. IFNalpha-treated HMC-1 cells expressing axl formed large cell aggregates within 40 h while untreated cells did not. HMC-1 cells also expressed gas6, the putative ligand of axl, which has been shown to induce axl-mediated homotypic binding. Gas6 expression was independent of interferon treatment in HMC-1 cells. The present results suggest that axl-mediated changes of cellular adhesive properties in mast cells may be important in mast cell differentiation as well as in mast cell-associated inflammation.