Transforming growth factors (TGFs) are defined as biologically active polypeptides which reversibly confer the transformed phenotype onto untransformed cultured cells. TGF-alpha shows sequence homology with epidermal growth factor and competes with epidermal growth factor for binding to the epidermal growth factor receptor, stimulating the phosphorylation of the receptor. TGF-alpha is secreted by many transformed cells and may be involved in embryonic development. A cloned human TGF-alpha gene was used to map the locus for the TGF-alpha precursor to the short arm of human chromosome 2, region 2p11----2p13, by Southern blotting techniques with DNA prepared from rodent X human somatic cell hybrids. These hybrids contained different subsets of human chromosomes and included a set with a translocation between human chromosomes 1 and 2 [t(1;2) (q32;q13)]. In situ hybridization of the TGF-alpha probe to normal human metaphase spreads confirmed these data and localized TGF-alpha more precisely to bands 2p11----2p13. Breakpoints in the variant Burkitt lymphoma translocation t(2;8) occur within these bands. Such a t(2;8) translocation could place TGF-alpha next to c-myc in band 8q24. The possibility is raised that TGF-alpha might contribute to tumor progression in these cases of Burkitt's lymphoma.