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Peripheral blood monocytes are attracted from the circulation to sites of active inflammatory bowel disease. This study sought to determine the role of monocyte-attracting chemokines in inflammatory bowel disease by examining the contribution of the α chemokine interferon-inducible protein-10, and the β chemokines, macrophage inflammatory proteins-1α and -1β and RANTES (Regulated on Activation, Normal T Expressed and Secreted) by using in situ hybridization and immunohistochemistry. Resected colonic tissue was obtained from five patients with ulcerative colitis, nine patients with Crohn's disease, and six with uninflamed mucosa remote from resected colon cancers. In situ hybridization by using riboprobes demonstrated that all four chemokines were expressed by macrophages, T lymphocytes, and endothelial cells in actively inflamed tissue but rarely expressed in uninflamed sections from inflammatory bowel disease or cancer-bearing colons. The frequency of chemokine-expressing cells was significantly greater in severely inflamed than in moderately or mildly inflamed tissue. RANTES was expressed by T lymphocytes in normal colon lamina propria, although infrequently. Granulomas were present in four Crohn's disease resections, and each of the chemokines was expressed by T cells and macrophages in loosely formed granulomas. Immunohistochemistry for macrophage inflammatory protein-1α confirmed the in situ hybridization findings: protein was associated with macrophages, T lymphocytes, and endothelial cells in actively inflamed colon. This study implicated a range of chemokines known to attract monocytes and subsets of T lymphocytes in the pathogenesis of inflammatory bowel disease and suggested significant redundancy in the generation of chemotactic signals in chronic inflammation.