We describe here the cloning and characterization of the human gene ERMAP, identified by subtractive hybridization using early and late gestation human fetal liver. By in situ hybridization, we found human ERMAP to be expressed not only in erythoid cells in fetal liver and adult bone marrow, but also in reticulocytes and circulating erythroblasts in 8-12-week fetal cord blood. The human ERMAP protein is predicted to contain a transmembrane segment and one extracellular immunoglobulin fold (IgV). The cytoplasmic region contains a highly conserved B30.2 motif, multiple consensus sequences for kinases, and post-Golgi sorting signals. The protein was localized to the cell surface as shown by an antibody specific for a peptide predicted from the IgV fold. The amino acid sequence of human ERMAP is highly homologous with that of mouse ERMAP, but differs in the number of extracellular immunoglobulin folds. Human ERMAP represents a new unique member of the rapidly growing B30.2 domain proteins.