The effect of synthetic surfactants and their binary mixture with a physiologic one, sodium taurocholate (STC), on the intestinal absorption of drugs was examined in rats by using the in situ recirculation technique. Synthetic surfactants investigated in this study were nonionic polysorbate 80 (PS-80), cationic cetyltrimethylammonium bromide (CTAB), and anionic sodium lauryl sulfate (SLS). The surfactant action on the mucosal membrane seemed to be the same magnitude as the stronger one of the two components, except in the case of CTAB, as estimated by the enhancement effect on sulfaguanidine absorption. The action of CTAB was increased in the presence of STC. The action of surfactants in the aqueous solution, an intraluminal action, was examined by using quinine as a model drug. The micellar interaction of the drug with an ionic surfactant, CTAB or SLS, was reduced by the addition of STC, whereas, that with a nonionic surfactant, PS-80, was increased as estimated by a dynamic dialysis technique. The inhibitory effect on quinine absorption was approximately proportional to the degree of the micellar complex formation. Two other model drugs, imipramine and sulfadimethoxine, were further examined and the possible mechanisms of these effects were discussed.