Glycophorin C (GPC) and D (GPD) are minor glycoproteins which are believed to be important for the structural integrity of the red cell membrane. We have investigated the structural relationship between these glycoproteins by both immunological and structural investigations: 1. A rabbit anti-serum produced against GPD reacts strongly with GPC and the abnormal glycoproteins of Gerbich: -2, -3 and Gerbich: -2,3 red cells, and recognizes most probably the homologous C-terminal portions of GPC and GPD. The two molecules however differ at their N-terminus. 2. One-dimensional mapping of the peptides obtained after tryptic, chymotryptic, V8 protease or acid cleavage of 125I-labelled GPC and GPD, indicated that GPC and GPD are structurally related but some differences were found indicating that additional peptides were generated from GPC. 3. The partial primary structure of GPD was determined. The sequencing data are consistent with the assumption that GPD represents an abridged version of GPC that comprises residues approximately 21/29-128 and exhibits a N-terminal residue that is blocked by an as yet undefined group.