Recent studies in mice have highlighted the importance of polymorphic genetic loci such as the major histocompatibility complex (MHC) or minor lymphocyte-stimulating antigen (Mls) in determining the nature of the peripheral T-cell receptor (TcR) population. As our knowledge of the equivalent process in humans is incomplete, we have utilized a modification of the polymerase chain reaction (PCR) to determine the overall genetic contribution to the normal human TcR variable V beta gene repertoire. These data demonstrate that the normal human T-cell population contains members of all the major TcR V beta families and that there is considerable variation in the relative amounts of specific TcR V beta transcripts between individuals. We have established that the normal peripheral TcR V beta repertoire is more concordant in identical twins than in unrelated individuals. The relative importance of genetic factors in determining the peripheral TcR repertoire is emphasized by these results and suggests that, in humans, the genetic control of immune responsiveness is mediated in part by the peripheral TcR repertoire.