The variable portion of an immunoglobulin heavy chain gene is assembled from at least three discontinuous segments of DNA, the V, D and J regions. We have characterized a 30 kb segment of the human genome that plays a critical role in the formation of this variable region as well as in the expression of the two heavy chains that appear earliest in immunocyte ontogeny, the mu and delta chains. This region encodes nine J-like segments, an interspersed D segment, recombination signals and the genes responsible for the production of both mu and delta heavy chains. Six of the nine germline J-like genes appear to be active and easily account for most of the known human heavy chain amino acid sequences. Three of the J-like genes are pseudogenes. The large number of human J region genes and, hence, their greater potential for generating diversity as compared to the that of the mouse J region genes appears to result from recent genetic duplications. To assess this potential, we have analyzed two recombinant genes involving this region. One of these, a V-D-J recombinant, is likely to be an active gene; the other, an aberrant D-J recombinant. A comparison of the structures of these D regions raises the possibility that they are mosaics formed by recombination between D segments.