Suspensions of colonocytes (isolated colonic epithelial cells) were prepared from mucosa of the descending colon from 6 patients with quiescent ulcerative colitis (UC), 4 with acute UC, and 7 control subjects. In each group metabolic performance was investigated by assessing utilisation of n-butyrate, the main respiratory fuel of the colonic mucosa, as well as utilisation of glucose and glutamine. In both acute and quiescent UC oxidation of butyrate to CO₂ and ketones was significantly lower than in the control tissues, and the decrease correlated with the state of the disease. Enhanced glucose and glutamine oxidation compensated for decreased butyrate oxidation in UC, indicating that colonocytes in colitis were not metabolically degenerate cells. Failure of butyrate oxidation reflects a variable yet definite metabolic defect in the mucosa in UC. Diminished oxidation of butyrate can explain the characteristic distribution of colitis along the colon, especially the frequency of UC in the distal colon. It is suggested that failure of fatty-acid (n-butyrate) oxidation in UC is an expression of an energy-deficiency disease of the colonic mucosa.