Nutrition of colonic epithelial cells (colonocytes) is maintained by luminal short-chain fatty acids (SCFAs), chiefly by n-butyrate. The importance of SCFAs for the maintenance of colonic epithelium has been demonstrated in animal models of colitis produced by rectal instillation of an inhibitor of SCFA oxidation and in patients with diversion colitis in whom a segment of colonic epithelium was deprived of contact with luminal SCFAs. We measured fecal SCFAs and lactate in children with ulcerative colitis (UC; n = 17) and with Crohn's disease with ileocolonic involvement (CD; n = 22) and age-matched controls (n = 12) by a vacuum-distillation, gas chromatographic method. Fecal SCFA concentrations were correlated with scores of clinical disease activity. Patients with UC and CD had a decrease in the fecal concentration of acetate (p < 0.05) and an increase in n-butyrate (p < 0.01) compared with controls. No significant changes in fecal lactate were seen. A comparison of inactive- or mild-UC patients with moderate or severe-UC patients yielded major differences in SCFA concentrations with n-butyrate increased in inactive and mild UC well above control values and total SCFA and acetate decreased in moderate and severe UC below control levels. Raised concentrations of fecal n-butyrate may reflect impaired utilization of this SCFA in the colon of patients with mild UC and Crohn's disease with colonic involvement. Whether this defect is primary or secondary to inhibitors in the colonic lumen, due to impaired transport of n-butyrate into the cell or defective metabolism within the cell, or specific to inflammatory bowel disease remains to be explored.