An interferon-inducible cytokine, IP-10, containing homology to a family of proteins having chemotactic (platelet factor 4, beta-thromboglobulin) and mitogenic (connective tissue-activating peptide III) activities has been mapped to chromosome 4 at band q21, a locus associated with an acute monocytic/B-lymphocyte lineage leukemia that exhibits the nonrandom translocation t(4;11)(q21;q23). In situ hybridization of t(4;11)(q21;q23)-carrying leukemic cells revealed that the IP-10 gene is proximal to the breakpoint of this translocation. No DNA rearrangement was evident when the IP-10 gene was hybridized to genomic DNA isolated from two patients' leukemic cells that contain t(4;11)(q21;q23). However, restriction fragment length polymorphism in the 5' region of the IP-10 gene was detected. The ETS1 protooncogene is located at 11q23 and is known to translocate to chromosome 4 in t(4;11) (q21;q23) and into the interferon gene cluster in (9;11) (p22;q23). Both translocations are associated with acute monocytic leukemia. These results suggest a model in which juxtaposition of genetic loci regulated by antiproliferative signals, such as interferon, next to an oncogene, like ETS1, could effectively short circuit homeostatic control circuits and contribute to the neoplastic state.