Glycophorin, the major glycoprotein of human erythrocytes, has been isolated and reincorporated into lipid vesicles. Freeze-fracture electron microscopy shows the reincorporated glycophorin to occur as small particles in vesicle fracture faces while the etch faces are smooth. The glycoprotein has a tendency to cluster into groups of several particles. Evidence is presented that, although lipids in immediate contact with glycopherin are likely somewhat immobilized, the entire lipid-protein complex has a tendency to occupy fluid regions of the bilayer. Reincorporated glycophorin assumes its proposed conformation in the intact erythrocyte in so far as it penetrates the hydrophobic membrane interior while its N-terminal end with attached carbohydrate residues is exposed to the aqueous compartment and is available as a specific recognition site.