To identify disease-specific T cell changes that occur in Crohn's disease (CD), the T cell receptor (TCR) BV repertoires of lamina propria lymphocytes (LPL) isolated from the diseased colon of seven CD patients and eight controls were determined by semiquantitative polymerase chain reaction (qPCR). As an internal control for the effects of HLA and other genes on the TCR repertoire, the BV repertoires of peripheral blood lymphocytes (PBL) from the same individuals were similarly determined and used for comparison. It was observed that the BV repertoires of LPL and PBL within the same individual were very different in both the CD and control groups. However, the CD4+, but not CD8+, repertoires of LPL and PBL differed to a much greater extent in the CD group than in the control group. Furthermore, in each CD patient there was a unique pattern of BV segments which were increased in the CD4+ LPL repertoire relative to that in PBL. These observations suggest that the inflammatory process in CD involves responses by specific CD4+ T cells to specific antigens. The isolation of such inflammation-specific CD4+ T cells may make it possible to identify the antigens which are responsible for the inflammatory process in CD and provide a better understanding of its pathogenesis.