Using a phage lambda Charon 4A recombinant DNA clone (lambdaCH4A-rHs18) from a human genomic library, Wyman and White detected a multiallelic common polymorphism at an EcoRI site (D14S1) flanking the DNA region homologous to the probe [Wyman, A. R. & White, R. (1980) Proc. Natl. Acad. Sci. USA 77, 6754-6758]. Subsequent studies, carried out with the cell hybrid approach and the use of a subclonal derivative (pAW101) from lambdaCH4A-rHs18 have assigned this locus to autosome 14 between 14q21 and 14qter [De Martinville, B., Wyman, A. R., White, R. & Franke, U. (1982) Am. J. Hum. Gen. 34, 216-226]. The data presented here permit the precise mapping of this locus to the subtelomeric region of autosome 14, below band 14q32, in close proximity to the heavy chain gamma1 immunoglobulin locus. These conclusions are supported by three independent lines of evidence, including studies on gene dosage, somatic cell hybrids, and pedigree analysis. Our results are in agreement with the recent assignment of the heavy chain gamma1 immunoglobulin locus to band 14q32 [Kirsch, I. R., Morton, C. C., Nakahara, K. & Leder, P. (1982) Science 216, 301-303] and are consistent with the generally held contention that one unit of meiotic recombination corresponds approximately to one million base pairs. It is to be expected that the location of the highly polymorphic D14S1 site at a measurable distance from the cluster of the heavy chain genes will provide new opportunities for a genetic approach to the question of the specific gene order within the cluster, its possible individual variation, and its biological significance in normal development and disease. It is worthwhile to point out that such a highly polymorphic DNA sequence is located in the same chromosomal region where so much somatic rearrangement goes on normally (i.e., switch region between classes of heavy chain constant region genes) and which is involved with de novo translocations associated with malignancies.