A noninvasive technique for determining bile acid kinetics by isotope dilution in man features the intravenous injection of a radiolabeled bile acid, together with daily oral administration, for several days, of capsules of dialysis membrane containing cholestyramine and colored beads for dating. The cholestyramine traps conjugated bile acids during transit of the small intestine. Capsules are recovered from stool by sieving, sequestered bile acid is eluted, conjugated bile acids are isolated chromatographically, and their specific activity is determined. The precision and validity of this sequestering capsule technique were assessed by comparing the specific activity decay curve of chenodeoxycholyl conjugates obtained from capsule samples with that obtained from duodenal samples in seven healthy volunteers in whom the bile acid pool had been labeled with [14C]chenodeoxycholic acid. Estimates of pool size by the two methods correlated well (r = 0.98), as did the daily fractional turnover rate (r = 0.96). The mean (+/-SD) percentage differences for the kinetic parameters of pool size (8.3 +/- 13.6), fractional turnover rate (-15.2 +/- 11.5), and synthesis rate (-4.3 +/- 11.4) were fairly small, indicating that the noninvasive method has validity. However, agreement between simultaneously administered capsules was only fair, especially when the amount of bile acid trapped was small, suggesting that the precision of the capsule technique may be less than that of the conventional duodenal sampling technique; the latter probably obtains a more valid sample of the bile acid pool.