To determine if organic anions contribute to the diarrhea of inflammatory bowel disease, we measured osmolality, electrolytes, short-chain fatty acids, lactic acid, and some Krebs cycle anions in 24-hr fecal collections from 18 patients with chronic ulcerative colitis, 20 with Crohn's disease of the colon, and 16 normals. Mean lactic acid concentration was significantly elevated in ulcerative and Crohn's colitis, but values correlated with fecal weight only in the former syndrome. In ulcerative colitis, concentrations of each short-chain fatty acid, especially butyrate, were decreased compared with those from normals or Crohn's disease. Lactate and short-chain fatty acids accounted for nearly half the variability in fecal weight in ulcerative colitis. Crohn's patients had elevated mean fecal water osmolality and osmotic gap not observed in ulcerative colitis. Increased lactic acid and/or deficient short-chain fatty acids may modulate the diarrhea of ulcerative colitis. This mechanism seems less important in Crohn's colitis where an additional osmotic component may be significant.