The leukocyte common antigen is a family of glycoproteins uniquely expressed by cells of hemopoietic origin. The family is generated by alternative splicing of 3 exons, and individual members are expressed in a cell type-specific fashion. The glycoprotein consists of a heavily glycosylated exterior domain of approximately 100 kDa, a single membrane spanning region, and a cytoplasmic domain that has homology to a protein tyrosine phosphatase of 83 kDa. To further understand the regulation and structure of this family of molecules, genomic clones were isolated from mouse lambda and cosmid libraries. The genomic organization was determined from 20 genomic clones. Eighteen of the clones clustered within a 75-kilobase region, whereas the promoter region, the exons for the 5'-untranslated region, and the leader domain are located an unknown distance further 5' within in an unlinked clone. The gene is composed of 34 exons: two 5'-untranslated exons, 1a and 1b, and 32 exons that encode protein sequence. Exon 2 contains part of the 5'-untranslated region and encodes the 23 amino acids of the leader sequence. Exons 3-15 encode amino acid residues 1-538 of the external domain, exon 16 encodes residues 539-574, encompassing the membrane-spanning domain, and exons 17-33 encode residues 575-1268 of the cytoplasmic domain. Exon 33, the largest exon, contains the 1.1-kilobase 3'-untranslated region. A comparison between mouse and human (Hall, L.R., Streuli, M., Schlossman, S.F., and Saito, H. (1988) J. Immunol. 141, 2781-2787) promoter regions reveals significant homologies 5' to the transcription start site. The relationship between exon structure and glycoprotein structure is discussed.