Fermentable dietary fiber components are known to stimulate colonic crypt proliferation. As these compounds are rapidly degraded to short-chain fatty acids (SCFAs) by the anaerobic microflora, the hypothesis was tested that this trophic effect of fiber may be mediated by SCFAs. Biopsies were taken from normal cecal mucosa of 45 individuals during routine colonoscopy. They were incubated for 3 hours with sodium salts of SCFAs at physiological concentrations (three SCFAs = acetate 60 mmol/L + propionate 25 mmol/L + butyrate 10 mmol/L; acetate 60 mmol/L; propionate 25 mmol/L; butyrate 10 mmol/L) or equimolar NaCl (control). Cell proliferation was measured autoradiographically by subsequent pulse labeling with [3H]thymidine (1 hour). The labeling index (number of labeled cells divided by the total number of cells) was computed for the crypt as a whole and for five equal crypt compartments (compartment 1 = crypt base, compartment 5 = crypt surface). Cecal crypt proliferation was raised significantly in all incubation experiments with SCFAs. Butyrate (10 mmol/L, increase + 89%) and propionate (25 mmol/L, + 70%) were as effective in stimulating proliferation as the combination of three SCFAs (+103%), although the effect of acetate (+31%) was minor. Increasing the butyrate concentration to 25 mmol/L or 60 mmol/L did not result in a further increase of cell labeling. SCFAs stimulated proliferation in the basal three crypt compartments only. An expansion of the proliferative zone to compartments 4 and 5 was not observed. SCFAs, especially butyrate and propionate, are luminal trophic factors for the cecal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)