When raw wheat bran was added to the diet of six subjects for 4-6 weeks, chenodeoxycholate (CDC) synthesis increased from 0.46 +/- 0.12 to 0.57 +/- 0.17 mmol/day pool increased from 1.72 +/- 0.47 to 2.19 +/- 0.74 mmol (rho less than 0.05). Deoxycholate (DC) pool size diminished from 1.20 +/- 0.29 to 0.80 +/- 0.16 mmol, but cholate synthesis and pool size were unaffected. Overall, the size of the bile salt pool did not change. In spite of this, when 10 patients with probable cholesterol gallstones took bran supplements for 4-6 weeks, their gallbladder bile aspirated from the duodenum became less saturated with cholesterol. The molar percentage of cholesterol fell from 10.1 +/- 3.1% to 8.6 +/- 2.7% (rho less than 0.01), and the saturation index of bile fell from 1.49 +/- 0.40 to 1.29 +/- 0.38 (rho less than 0.005). Bran probably operates primarily on the colon, reducing the formation or absorption of the bacterial metabolite DC, a substance which impairs CDC synthesis.