Both acute myeloid leukemia 1 and c-Fos are regulatory factors of hematopoietic cell differentiation. We identified that the c-fos promoter contains an acute myeloid leukemia 1 binding site at nucleotide positions -6-+14. c-fos promoter activity was induced by transient overexpression of acute myeloid leukemia 1 in Jurkat T-cells, but not by that of the short form of acute myeloid leukemia 1-MTG8, a chimeric acute myeloid leukemia 1 protein. In 32Dcl3 myeloid cells, stable overexpression of acute myeloid leukemia 1-MTG8 blocked the c-fos gene transcription and cell differentiation, but that of acute myeloid leukemia did not. These data suggest that acute myeloid leukemia 1 and acute myeloid leukemia 1-MTG8 reciprocally regulate the myeloid cell differentiation, possibly by the way of regulating c-fos gene transcription.