Isothermal titration calorimetry (ITC) was used to investigate the interactions of bile salts with phosphatidylcholine vesicles. We determined the partition coefficients of the detergents sodium cholate (NaC) and sodium deoxycholate (NaDC) and the respective transfer enthalpies between pure water or 0.1 M aqueous salt solution and bilayers, consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC). Additionally, the vesicle-to-micelle transition was investigated for NaC/DPPC and NaDC/DPPC systems in water and 0.1 M NaCl. ITC was employed to determine the phase boundaries for the saturation and the complete solubilization of the vesicles by the bile salts enclosing the coexistence region of mixed vesicles and micelles. To study the influence of the alkyl chain length of the phospholipids on the phase behavior we also studied the NaDC/DMPC system. Saturated phosphatidylcholines are more easily transformed into micelles than those with unsaturated chains. In the region of low lipid concentrations we observed a departure from linearity of the phase boundaries, which was explained by the influence of the energy of end-caps as proposed by Roth et al. (Langmuir 2000, 16, 2052). The deviation was larger for systems in pure water compared to those in 0.1 M NaCl. The saturation concentrations of bilayers of DPPC and DMPC were much lower than those for unsaturated analogues. The saturation concentration increased with increasing salt content, and the coexistence range became wider. The ITC solubilization curves could be analyzed by applying the known values for partition coefficients and transfer enthalpies for the detergents to the different types of aggregates.