The architecture of the murine VCAM1 gene, encoding vascular cell adhesion molecule-1, was determined. Its 10 exons span approximately 20 kb. Exon 1 encodes the 5′ untranslated region and the signal peptide; exons 2-4 and 6-9, the C2 or H-type immunoglobulin domains; and exon 10, the transmembrane and cytoplasmic domains followed by the entire 3′ untranslated region. All immunoglobulin-like domains are encoded by separate exons, and exon splice junctions occur after the first nucleotide of amino acid codons (type 1). Exon 5 encodes a novel domain unique to murine VCAM-1 and inclusion of this exon by alternative splicing results in a truncated three-immunoglobulin-like domain form, which is bound to the cell membrane by a phosphatidylinositol linkage at its carboxy terminus (encoded by exon 5). The murine VCAM1 core promoter contains a high degree of homology to the human, including conserved consensus binding sites for NF-κB, the Ets class, and the GATA family of transcription factors, suggesting that the murine and human VCAM1 genes may be under similar transcriptional control.