The cDNA clone for a major mouse glycophorin, transmembrane glycoprotein of erythrocytes has been isolated from a mouse spleen erythroblast cDNA library. The primary structure of a major glycophorin indicates that the protein is a single polypeptide chain of 168 amino acids (aa) clearly organized in three domains distinct in the glycophorin of other species. A strong homology of the mouse major glycophorin with human glycophorin A or B, but not with human glycophorin C is observed only in the hydrophobic stretch of 23 nonpolar aa, indicating that the major mouse glycophorin species cloned is similar to human glycophorin A. The glycophorin mRNA is absent in all non-erythroid organs or cell lines examined. The glycophorin mRNA is induced during the differentiation of murine erythroleukemia cells with dimethyl sulfoxide.