The dependence of cells of the colonic epithelium upon lumenal short-chain fatty acids (SCFA) for some of their energy supply is well known. SCFA (mainly acetic, propionic, and n-butyric acids) comprise the predominant solutes in the aqueous phase of colonic contents and are produced by anaerobic bacterial fermentation of polysaccharides. Acetic acid is the principal fatty acid, but n-butyric acid is the preferred energy source for colonocytes, both in normal human colon and in colons of patients with ulcerative colitis. Four patients with diversion colitis, an inflammatory process in surgically excluded colon and rectum, were successfully treated by colonic instillation of a solution of mixed SCFA. This review examines the evidence that diversion colitis may be a new type of nutritional-deficiency syndrome based upon a local mucosal requirement for SCFA.