We have compared the frequencies of T cells expressing each of four different T cell receptor (TCR) Vβsegements in lamina propria and peripheral blood lymphocytes of 12 Crohn's disease (CD), six ulcerative colitis (UC), and 10 control patients in an attempt to identify disease-specific changes. The frequencies of CD4 + and CD8 + cells reacting with each of four fluoresccinated TCR-specific monoclonal antibodies directed against Vβ5, Vβ6.7a, Vβ8, and Vβ12 were determined by flow cytometry. There was no difference among the groups in the average frequency of any single Vβsegment in either the CD4 + or CD8 + subpopulations. However, when the sum of the differences in VP frequencies (Δscore) between peripheral blood lymphocytes (PBL) and lamina propria lymphocytes (LPL) were determined for each individual, significant differences were observed between the CD4 + and CD8 + populations and among the patient groups. In all three patient groups, there were significant individual differences between LPL and PBL in the frequencies of CD8 + and CD4 + cells reacting with the four Vβ-specific mAb. In Controls and UC, this difference was, on average, two-fold greater in CD8 + cells than in CD4 +. In CD, however, this difference was, on average, the same for CD8 + and CD4 + cells. These observations suggest that (1) the human colonic LPL TCR repertoire is normally different from that of PBL, especially in the CD8 + population and (2) there is an alteration in the LPL TCR repertoire in CD which is not observed in Controls or UC.