A primary metabolic disorder may be present in the colonic mucosa of patients with ulcerative colitis. Preserving the epithelium in situ, we evaluated the metabolism of the colonic mucosa of control patients and patients with ulcerative colitis and Crohn's disease. Colonic mucosal strips (~500 mg) were incubated with partially ¹⁴C-labeled acetate (C₂), butyrate (C₄), hexanoate (C₆), octanoate (C₈), and glucose, and the production of CO₂ and ketone bodies was quantitated. Metabolism by small intestinal mucosal strips was also evaluated. Compared with controls, no decrease in either CO₂ or ketone body production by colonic strips from patients with either ulcerative colitis or Crohn's disease was observed for any substrate. The CO₂ production from each of the C₂-C₈ fatty acids was the same for colonic and small intestinal strips, whereas CO₂ production from glucose was higher in small intestinal strips than in colonic strips. The production of ketone bodies was low in small intestinal strips. A primary metabolic disorder in the colonic mucosa of patients with inflammatory bowel disease was not found.