The majority of y/8 T cell receptors (TCR) in the humanIntestinal mucosa are thought to use the TCRDV1 (V81) variable region gene segment, whereas y/8 T cells in the circulation predominantly express the TCRDV2 (V82) gene segment. 8 T cell receptors that use the TCRDV2 variable region gene segment generally have been regarded as highly diverse, whereas those that use the TCRDV1 gene segment are oligoclonal, whether present in the intestinal tract or in peripheral blood. We report herein that oligoclonality is a genal feature of the peripheral 8 T cell receptor repertoire In heWthy human adults, irrespective of the variable region used and regardless of whether y/8 T cells reside in the intestinal mucosa or in peripheral blood. In addition, the 8 T cell receptor repertoire is shown to be highly compartmentalized between such sites as the colon and peripheral blood, relatively stable over at least a 10-16-mo period, and unique in each individual. Further, the spectrum of variable region genes used by 8 T cell receptor transcripts in the human c.Ia is greater than previously recognized. Thus, in additin to the TCRDV1 and TCRDV2 variable region gene segments, 8 T cell receptors in normal intestinal mucosa can use TCRDV3 (V83) and TCRAV (Va) gene segments which, in some individuals, comprise a significant component of the mucosal 8 T cell receptor repertoire. Our studies indicate that the potential of 8 T cell receptors for extensive diversity is not reflected in the mature human repertoire. Moreover, these findings suggest a model wherein the 8 T cell receptor repertoire in the colon and peripheral blood is aped by selection and clonal expansion of y/v T cells that thuwtely seed throughout the length of the colon mucosa and populate the circulation. (J.