Fecal concentrations of short-chain fatty acids were markedly reduced in 6 patients with pouchitis (mean +/- SE, 56.2 +/- 13.3 mmol/L) compared with 28 patients without pouchitis (139.0 +/- 8.5 mmol/L; P less than 10(-3)). The ratios of acetate to propionate to butyrate were not changed (pouchitis, 75:12:11%; normal pouches, 76:12:11%), i.e., all acids were equally reduced. The 24-hour production of total short-chain fatty acids in 16.6% fecal homogenates from patients with pouchitis was decreased (17.5 +/- 5.3 mmol/L) compared with patients without pouchitis (33.3 +/- 3.4 mmol/L; P less than 0.05), which could be overcome by the addition of saccharides to the homogenates. Pouch excretions of saccharides were similar in the two groups, but dilution occurred during pouchitis because of the increased outputs. Concentrations and productions of short-chain fatty acids correlated with pouch concentrations and excretions of sodium and saccharides. L-Lactate was elevated in pouchitis outputs, but differences in stool culture counts, mucosal histology, fecal concentration, assimilation or production of ammonia, nitrogen excretion, pH, and osmolality were not found. Pouchitis is characterized by decreased fecal concentrations and productions of short-chain fatty acids possibly caused by low pouch concentrations of fermentable saccharides.