Solvation free energies of drugs, peptides, and other small molecules in the core and headgroup regions of phospholipid bilayers determine their conformations, accumulation, and transport properties. The transfer free energy includes the energy terms for the formation of a cavity for the solute, the interactions of the solute with phospholipids, electrostatic interactions of the solute with the membrane, and dipole potentials and entropy terms. The interaction energies with phospholipids can be estimated by correlating the partitioning in Surrogate solvent systems and in the bilayer. As the head-roup surrogate, we use diacetylphosphatidylcholine (DAcPC), the acetylated headgroup of the most abundant mammalian phospholipid, phosphatidylcholine, which forms a homogeneous solution with acceptable viscosity when mixed with water in ratios similar to those in the fully hydrated bilayer. The two-phase system of n-hexadecane (C16) as the core surrogate and hydrated DAcPC was used to monitor partitioning of 16 nonionizable compounds. Oil the bilogarithmic scale, the C16/DAcPC partition coefficients correlate neither with those in the C16/water and l-octanol/ water systems nor with their difference, which is frequently used as a parameter of hydrogen bonding for prediction of the bilayer location of the solutes. The C16/DAcPC system provides a satisfactory einulation of the solvation properties of the bilayer regions, as reflected in correct predictions of the bilayer location for those of the studied chemicals, for which this information is available.