The gene for human leukemia inhibitory factor (LIF) has been mapped by Southern analysis of a series of mouse/human somatic cell hybrids and by in situ hybridization to the chromosomes of two normal males and some individuals with chromosomal rearrangements. The gene maps to 22q11-q12.2, between the Philadelphia translocation BCR gene and the breakpoint of the translocation in cell line GM2324 at 22q12.2. From the grain distribution over high resolution chromosome preparations, the most likely location is 22q12.1----q12.2. Southern analysis of DNA from one Ewing sarcoma with t[11;22][q24;q12] showed that the breakpoint on chromosome 22 is more than 15 kb 5' or 8 kb 3' from the LIF gene. The location of the LIF gene indicates that translocations of this gene are unlikely to play a role in myeloid leukemia and myeloproliferative disorders.