Glycophorin C (GPC) is an integral membrane protein of human erythrocytes which plays an important role in regulating the deformability and mechanical stability of red cells. Recently, the structural gene for this glycoprotein has been cloned (Colin, Y., Le Van Kim, C., Tsapis, A., Clerget, M., d'Auriol, L., London, J., Galibert, F., and Cartron, J. P. (1989) J. Biol. Chem. 264, 3773-3780), and we have now determined the sequence of the 1050 base pairs of DNA preceding the transcription initiation site mapped in erythroid cells. This region contains different potential regulatory cis-acting elements found in a variety of eukaryotic promoters (TATA box, CAAT box, Sp1-binding site) as well as sequences present in the promoter and enhancer regions of genes specific for the erythroid lineage (CACCC box and NF-E1-binding site). Northern blot analysis and immunological studies indicate that the GPC gene is expressed in a large number of cells and tissues. However, the level of transcription as well as the glycosylation of the mature GPC differ in erythroid and nonerythroid cells. Primer extension analysis and mapping of the 5' end GPC mRNA by the polymerase chain reaction indicate that different transcription sites are utilized for the expression of the GPC gene in erythroid and nonerythroid tissues and cell lines.