Mucosal macrophages have been implicated in the pathogenesis of inflammatory bowel disease (IBD). Macrophage-colony stimulating factor (M-CSF) influences monocyte/macrophage proliferation, differentiation, and activation. Serum levels are increased in active IBD, but little is known about its role in mucosal inflammation. This study was undertaken to determine the distribution, frequency, and level of M-CSF expression in normal and IBD-affected intestine. RNA and tissue were studied from patients with Crohn's disease (CD) and ulcerative colitis (UC) as well as from histologically normal colon. Tissue from intestinal tuberculosis and ischaemic colitis patients served as controls. M-CSF mRNA and protein were examined by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridisation, and immunohistochemistry, respectively. M-CSF mRNA and protein were detected in histologically normal intestine, but their expression was largely confined to the mucosa. In active IBD, the frequency of M-CSF-expressing cells was significantly increased and their distribution markedly altered, although no increase in mucosal M-CSF mRNA levels in intestinal tissue was observed. The changes were not specific to IBD, as there were similar findings in intestinal tuberculosis and ischaemic colitis. The marked alteration observed in M-CSF expression in IBD and the importance of this cytokine in stimulating macrophage functions suggest that M-CSF may contribute to the pathogenesis of the IBD lesion. Copyright © 2001 John Wiley & Sons, Ltd.