Stem cell factor (SCF) or c-Kit ligand is a cytokine associated with the differentiation, survival, and activation of mast cells. Eosinophils have pleiotropic functions in several diseases and, together with mast cells, are key cells in allergy. Mast cell-eosinophil interactions can take place during the late and chronic phases of allergy. It was, therefore, investigated whether eosinophils can produce SCF and consequently influence mast cells. Human peripheral blood eosinophils variably expressed mRNA for the soluble and uncleaved forms of SCF (reverse transcription-polymerase chain reaction) and produced the 18.5-kd protein backbone of SCF (Western blot analysis). After overnight incubation in medium, eosinophils also produced SCF of higher molecular weight (42-45 kd) that might represent its glycosylated forms. Eosinophils expressed cytoplasmic SCF that colocalized with major basic protein (confocal laser microscopy). Freshly isolated eosinophils contained 8.9 ± 1.7 pg SCF/106 (mean ± SEM; enzyme-linked immunosorbent assay). Although overnight incubation of the eosinophils in either culture medium or in phorbol 12-myristate 13-acetate-calcium ionophore did not cause the secretion of SCF, the addition of chymase induced SCF release. In summary, it was demonstrated that human peripheral blood eosinophils are a source of SCF. These results may contribute to a better understanding of the interactions between eosinophils and mast cells in allergic inflammation.