Expression of alpha 4 beta 7 on memory T lymphocytes identifies a cell population that preferentially migrates to the gut. Detection of alpha 4 beta 7 on circulating lymphocytes may permit the identification of specific subsets trafficking between the circulation and the gut in inflammatory bowel diseases. Samples and clinical details were taken from patients with Crohn's disease (CD), ulcerative colitis (UC), diverticulitis/ infectious colitis, and healthy controls. Peripheral blood and lamina propria mononuclear cells were isolated. Cells were labelled with CD3, CD4, CD25, CD45RO or alpha 4 beta 7. Median levels of circulating total memory T cells (CD4+CD45RO+) were increased in CD (p < 0.01) and UC (p < 0.05). However, the proportion of systemic gut homing T cells (CD4+CD45RO+ alpha 4 beta 7+) was decreased in CD (p < 0.05), UC (p < 0.002), and inflammatory controls (p < 0.05). Levels of activated gut homing T cells (CD4+CD25+ alpha 4 beta 7+) were increased in CD (p < 0.01) and UC (p < 0.05). For both CD4+CD45RO+ and CD4+CD25+ cells, the proportion of lymphocytes coexpressing alpha 4 beta 7 was decreased compared with controls. In small and large intestine lamina propria, expression of alpha 4 beta 7+ on CD3+ cells was extensive, although it was decreased in CD (p < 0.03), UC (p < 0.05), and inflammatory controls (p < 0.05). Circulating and mucosal gut homing lymphocyte populations are changed in patients with colonic inflammation. This may arise due to a dilution effect from recruited naive T cells, or from integrin down regulation. Changes in general CD4+ lymphocyte populations mask more subtle variations in those cells with gut homing potential.