The low aqueous solubility of phospholipids makes necessary the use of lipid carriers in studies ranging from lipid traffic and metabolism to the engineering of model membranes bearing lipid transverse asymmetry. One particular lipid carrier that has proven to be particularly useful is methyl-beta-cyclodextrin (M beta CD). To assess the interaction of M beta CD with structurally different phospholipids, the present work reports the results of isothermal titration calorimetry in conjunction with dynamic light scattering measurements. The results showed that the interaction of M beta CD with large unilamellar vesicles composed of a single type of lipid led to the solubilization of the lipid vesicle and, consequently, the complexation of M beta CD with the lipids. This interaction is dependent on the nature of the lipid headgroup, with a preferable interaction with phosphatidylglycerol in comparison to phosphatidylcholine. It was also possible to show a role played by the phospholipid backbone in this interaction. In many cases, the differences in the transfer energy between one lipid and another in going from a bilayer to a cyclodextrin-bound state can be qualitatively explained by the energy required to extract the lipid from a bilayer. In all cases, the data showed that the solubilization of the vesicles is entropically driven with a large negative Delta C-p , suggesting a mechanism dependent on the hydrophobic effect.