Glycophorin from the human erythrocyte membrane has been isolated in pure form and reconstituted into large unilamellar vesicles comprised of binary mixtures of 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC) and chain perdeuterated 1,2-dimyristoyl-3-sn-phosphatidylcholine (DMPC-d₅₄). The effect of temperature and protein on lipid structure and mixing was monitored by using Fourier transform infrared spectroscopy; deuteration of one of the components of the mixture permits observation of the protein interaction with each lipid species. The melting curves were analyzed by assuming that each lipid chain can exist in one of two physical states (Le., gel or liquid crystalline), characterized by a temperature-dependent Lorentzian distribution for the line shape of the C-H or C-D stretching vibrations. The fraction of each lipid component melted at temperatures within the two-phase region of the phase diagram was calculated and approximate phase diagrams were constructed. Addition of protein lowers the liquidus line of the phase diagram while leaving the solidus line essentially unchanged. No lipid phase separation is observed. The effect of protein is more pronounced on the DPPC component than on the DMPC-d₅₄.The former is significantly more disordered and/or fluidized at all lipid mole fractions in the ternary system than in the binary phospholipid mixture.