The intestinal absorption of bile acids is determined by two resistances: diffusion through an unstirred water layer and penetration of the cell membrane. Passive jejunal uptake of polar bile acids is limited by the mucosal membrane, whereas the unstirred layer exerts resistance on uptake of more nonpolar species. After correction for the diffusion layer, the membrane permeability coefficients were derived to calculate the delta delta Fw leads to 1 associated with uptake of the -OH (+874 cal.mol-1), glycine (+897), and taurine (+1,498) groups. The delta delta F1 (-6,126 cal.mol-1) for the -OH group suggested that the jejunal mucosa is a relatively polar membrane. The unstirred layer is even more rate limiting for bile acid uptake from micellar solutions. Once the micelle reaches the aqueous-membrane interface, it is not absorbed intact, but rather uptake is explained in terms of monomers in the aqueous phase that are in equilibrium with the micelle. The presence of the unstirred water layer introduces artifactually high Km values for active transport. Structure-activity studies suggest that the ileal recognition site consists of a component for the steroid moiety, a positive charge, and an adjacent anionic charge. The energy for active transport arises from the Na+ gradient across the brush-border membrane that, in turn, is dependent on the activity of Na+-K+-ATPase. The Na+ stimulation of bile acid transport across the ileal brush-border membrane is due to influx coupling via a cotransport system rather than electrical coupling to satisfy overall electrical neutrality.