The host-guest properties of a water-soluble resorcinarene cavitand bearing four guanidines at the feet were investigated in water and dodecylphosphocholine (DPC) micelles by NMR spectroscopy. While the binding of different guests in water was generally modest, the formation of the caviplexes was significantly enhanced in the presence of micelles and reached affinities typically observed for organic solvents. The increase in binding free energies of up to 3.2 kcal mol(-1) was determined to be enthalpic in origin and was attributed to the disruption of velcrand dimers and subsequent conformational reorganization of the receptor induced by the micelles that acted as hosts for the cavitand. In agreement with the NMR data, molecular dynamics simulations reproduced the spontaneous incorporation of the cavitand into the micelle and provided a detailed picture of the positioning of the receptor at the DPC-water interface.