Leukemia-inhibitory factor (LIF) and oncostatin M (OSM) are members of a family of structurally similar growth factors presenting overlapping and specific functions. Although the genes coding for IL-6, CSF3 and CNTF are scattered in the human and mouse genome, human LIF and OSM genes have conserved synteny in the course of evolution. Through isolation of a YAC and a cosmid clone containing both LIF and OSM we demonstrate that the two genes are linked in tandem on human chromosome 22q12, separated by 16 kilobases of intervening genomic DNA and transcribed in the same head-to-tail orientation. The close physical linkage between LIF and OSM genes brings new evidence of their evolutionary relationship.