The peripheral T cell receptor repertoire is mainly controlled by the processes of positive and negative selection occurring in the thymus. Studies in normal or transgenic mice have provided compelling evidence for both negative and positive selection. Negative selection is characterized by partial or total disappearance from the periphery of T cells expressing certain C beta regions, which are normally present in the thymus. Positive selection is chiefly characterized, in the periphery, by an imbalanced ratio between CD4+ and CD8+ T cells expressing a given V domain. To date little information concerning positive and negative selection has been available in man. We studied the distribution of 4 V beta domains on CD4+ and CD8+ peripheral T cells of 34 healthy individuals with a wide age-range (0-96 years). One of the V beta domain studied, V beta 6.7, is preferentially expressed on CD4+ compared to CD8+ T cells (p greater than 0.001). No significant differences were observed using the other V beta domain-specific monoclonal antibodies (V beta 5.2-5.3, 8 or 12). These results provide evidence that a process of thymic education, similar to that described in murine animal models, may also take place in man.