Analysis of the telomeric region of chromosome 14q has enabled us to complete a map of the immunoglobulin V_H locus which accounts for almost all V_H segments known to rearrange in B-lymphocytes. The human germline V_H repertoire consists of approximately 50 functional V_H segments — the exact number depending on the haplotype — spanning 1,100 kilobases upstream of the J_H segments. A yeast artificial chromosome used to map these segments was isolated by its ability to provide telomere activity in yeast, suggesting that the V_H locus may be located within a few kilobases of the 14q telomere. The limited structural diversity encoded by the functional V_H segments demonstrates the importance of combinatorial diversity produced by VDJ joining and the association of heavy and light chains in producing the human antibody repertoire.