It has been shown that a conserved but highly biased subset of the germline VH complement is utilized in the peripheral VH repertoire of Caucasians. To distinguish between VH-autonomous effects and background genetic effects, we have now assessed the incidence of rearrangement of eight VH3 gene segments in preimmune CD19+IgD+B cells from genetically disparate subjects of diverse ethnic backgrounds. Results indicate that the set of gene segments utilized for rearrangements by these subjects is similar, and predominantly reflects the bias previously observed in Caucasians. The preimmune repertoire of each subject is dominated by two or three gene segments, with a predominant expression of V3-23 in all the subjects. Variation in the use of individual gene segments, including V3-23, was observed among the subjects. These results indicate that the processes that favor the preferential use of particular genes is largely independent of genes outside the VH locus. The minor variation in utilization of VH segments, however, is probably influenced by the genetic background of the individual.