The human myeloperoxidase (MPO) gene has recently been cloned in our laboratory. Southern blot hybridization of our MPO cDNA to DNA from a somatic cell hybrid clone panel revealed that the MPO cosegregated with human chromosome 17. In situ hybridization mapped the MPO gene to chromosome 17q22-24. Although this location is close to the translocation breakpoint which occurs in acute promyelocytic leukemia (APL), t(15;17)(q22;q21-22), Southern blot hybridization with different restriction-digested genomic DNA samples from four APL patients did not reveal MPO gene rearrangement. However, RNA dot-blot hybridization showed that APL patients with the translocation expressed high levels of MPO mRNA. This observation raises the possibility that the high levels of MPO gene expression in APL could be due to the arrest of leukemic cells at a specific stage of differentiation or a consequence of the translocation.