We demonstrated the significant eosinophilic growth of leukemic cells in the presence of interleukin-5 (IL-5) in 2 of 15 cases of acute myeloid leukemia. These two cases were M2 (FAB classification) with the translocation (8;21)(q22; q22). Bone marrow examination revealed the rather high percentages (6% and 9%) of atypical eosinophils in the total nucleated bone marrow cells in these two cases. In the remaining 13 cases, eosinophils were less than 2% in the nucleated bone marrow cells. In the methylcellulose culture system, 142 +/- 18 or 54 +/- 2 colonies were formed by 5 x 10(4) mononuclear cells in the presence of IL-5 in these two cases. These colonies mainly comprised mature eosinophils. Eosinophils were confirmed by Biebrich scarlet staining and electron microscopic examination using a specific lectin binding assay. The eosinophilic differentiation and proliferation of leukemic cells were also observed in the liquid culture system. It was shown that eosinophils observed in both systems were derived from leukemic cells using the chromosomal marker of leukemic cells, t(8;21). Leukemic cells also differentiated to neutrophils or both neutrophils and eosinophils in response to granulocyte colony-stimulating factor or interleukin-3, respectively, but did not respond noticeably to granulocyte-macrophage colony-stimulating factor. Although IL-5 acts on normal eosinophil committed precursors as a lineage-specific growth factor, at least some leukemic cells reacted to IL-5 and could proliferate and differentiate along eosinophilic pathway. Our findings suggest that atypical eosinophils observed in the bone marrow were derived from the leukemic clone in two cases of AML.