Short-chain fatty acids (SCFA) originate mainly in the colon through bacterial fermentation of polysaccharides. To test the hypothesis that SCFA may originate from polypeptides as well, the production of these acids from albumin and specific amino acids was examined in a faecal incubation system. Albumin was converted to all C2-C5-fatty acids, whereas amino acids generally were converted to specific SCFA, most often through the combination of a deamination and decarboxylation of the amino acids, although more complex processes also took place. This study indicates that a part of the intestinal SCFA may originate from polypeptides, which apparently are the major source of those SCFA (isobutyrate, valerate, and isovalerate) only found in small amounts in the healthy colon. Moreover, gastrointestinal disease resulting in increased proteinous material in the colon (exudation, mucosal desquamation, bleeding, and so forth) may hypothetically influence SCFA production.