Glycophorin can be incorporated in lipid vesicles without the use of detergents [MacDonald, R.J. and MacDonald, R.C. (1975) J. Biol. Chem. 250, 9206-9214]. In this paper it has been shown that the protein spans the lipid bilayer in these vesicles. In addition it has been shown that the protein is oriented in an asymmetric way with 75-80% of its sugar residues directed to the outside of the vesicles. Freeze-fracturing electron microscopy suggests that the protein is present in a slightly aggregated form. Sonication of these recombinants leads to the formation of small glycophorin-containing vesicles, in which almost all sugar residues are directed to the outside.