β7 Integrins have been shown to have an important role in the localization of T cells to the intestine. Utilizing two different experimental mouse models of inflammatory bowel disease (IBD), this study was undertaken to determine if β7 integrin expression is critical for T cell localization to the intestine and colitis pathogenesis. Transfer of CD4⁺ CD45RB^high cells into immunodeficient mice results in colitis. To examine the role of β7 integrins, donor cells were obtained from β7 integrin gene-deficient animals and disease induction was examined following transfer into severe combined immunodeficiency (SCID) mice. Additionally, β7 integrin gene-deficient animals were crossed to IL-2-deficient mice and the onset of spontaneous colitis that normally occurs in IL-2-deficient animals was examined. No differences in the onset or severity of spontaneous colitis was noted in animals that were deficient in both β7 integrin and IL-2. In contrast, the onset of colitis in recipients of T cells from β7 integrin-deficient donors was delayed significantly. In mice receiving β7 integrin negative cells, the initial lack of colitis appeared to correlate with fewer numbers of CD3⁺β7 integrin –/– donor lymphocytes present in the host colon. The eventual development of disease, however, was associated with increased numbers of donor β7 integrin –/– lymphocytes. These results show that β7 integrin expression is not absolutely required for T cell localization to the intestine and colitis pathogenesis.