Since 1939, a series of clinical reports and laboratory investigations have suggested that the intestinal fecal stream may play a significant part in the pathogenesis of Crohn's disease (CD). The beneficial effect of exclusion of the stream by ileostomy was followed by improvement in patients with CD of the ileum and colon despite little change in the histopathology of the excluded loop, even to the point of allowing restoration of intestinal continuity in some patients. End ileostomy lowers the risk of recurrence of CD compared with anastomotic operations. Ileostomy effluent can reactivate the clinical activity of quiescent bypassed bowel and some of its biochemical processes, and may be related to an ultrafilterable constituent > 5 microns. Experimental models of inflammatory bowel disorders in immunologically altered rodents (transgenic, knockout, or spontaneous) require the presence of normal luminal bacteria, especially of the Bacteroides species, and respond to antibiotic (metronidazole) therapy. Thus, many but not all of the well-recognized clinical features of CD are compatible with a pathogenetic role of the fecal stream. Although difficult to quantitate, this concept opens the way to a variety of testable research lines, and allows some speculation regarding its clinical implications.