The sharp demarcation between diseased and normal mucosa often observed in ulcerative colitis remains unexplained by current hypotheses of disease pathogenesis. To investigate whether this demarcation occurs at the watershed of vascular territories, the colonic arterial anatomy of 10 patients with ulcerative colitis was studied by in-vitro angiography and macroscopic and histological examination of total colectomy specimens. Of the 10 perfusion-fixed colectomy specimens studied, 7 had pancolitis associated with a complete marginal artery (Arteria marginalis coli) that spanned the entire length of the large bowel. 3 specimens had sharply demarcated disease in which the marginal artery arose from the inferior mesenteric artery and ended abruptly at the point of mucosal demarcation. The colon proximal to this point was histologically normal. These findings suggest that the proximal extent of colitis is determined by the limit of the marginal artery. We suggest that some characteristic of the mucosal microvasculature in the territory of the inferior mesenteric artery, possibly embryological in origin, predisposes the dependent colon to develop ulcerative colitis.