The solubilization of POPC lipid bilayers by the nonionic detergent C(12)EO(8) was studied by isothermal titration calorimetry. The characteristic transfer enthalpies for the detergent and the lipid between bilayers and micelles were determined by titration of detergent micelles to lipid membranes and vice versa. For purpose of comparison, the enthalpy and Gibbs free-energy changes for the aggregation of aqueous detergent monomers to micelles as well as for the partitioning into lipid bilayers were analyzed. The phase boundaries between pure bilayers and pure micelles, i.e., the detergent mole fraction, when the bilayers become saturated with detergent and first mixed micelles appear and the mole fraction when the bilayers are completely solubilized and only mixed micelles are present could be easily determined from the titration experiments. The detergent binding to membranes does not follow the mass action law because there are no specific binding sites. An equation using partitioning of detergent between water and bilayers gave good fits to the experimental data. The experiments lead to a consistent set of transfer enthalpies and entropies for the system of monomers, micelles, and bilayers. Suggestions are made about the thermodynamic nature of solubilization and partitioning. Finally, besides the limiting compositions of bilayers and micelles, another composition-driven transition was detected within the mixed micellar range. This can be imagined to correspond to a variation of the micellar shape and size and/or intermicellar interactions.