Benign rat mammary epithelial cells transfected with restriction enzyme-fragmented DNA from a human malignant metastatic cell line (Ca2-83) produces transfectants that yield metastatic tumours in syngeneic rats. The six metastasis-inducing DNAs (Met-DNAs) that have been isolated from such transfectants are subgene in size and do not code for any expressed mRNAs, but correspond to potential regulatory regions of human DNA from malignant, metastatic cells. In pilot studies the one Met-DNA tested is detectable in some human breast tumours but not in normal tissue. Transfection of all six Met-DNAs singly into the benign mammary epithelial cells causes enhanced expression of osteopontin, whilst transfection of cDNA for osteopontin also induces the metastatic state. These results show that short regulatory DNAs exist in human cancer cells that can induce metastatic spread via a common effector gene, osteopontin, in model rat mammary cell lines.