We have isolated cDNAs that complete the elucidation of the primary structure of the mouse alpha 1(XVIII) collagen chain, a polypeptide homologous to the alpha 1(XV) collagen chain. The 1315-residue alpha 1(XVIII) chain includes a 25-residue signal peptide, a 301-residue NH2-terminal non-collagenous domain (NC1), a 674-residue collagenous sequence with nine interruptions of 10-24 residues, and a 315-residue COOH-terminal noncollagenous domain (NC11). Seven of the collagenous domains and both flanking noncollagenous domains share homology with the alpha 1(XV) chain. The COOH-terminal noncollagenous domains are unique to the alpha 1(XVIII) and alpha 1(XV) chains, and they contain a homologous beginning, a variable portion, and a highly homologous COOH-terminal half with 4 conserved cysteines. The differences in the collagenous sequences probably preclude the existence of the two chains in the same molecule, however. A 12.5-kilobase pair genomic sequence was found to contain the 12 extreme 3'-exons of the alpha 1(XVIII) gene, covering 40% of the coding sequences. Exons start with either a complete codon or a split codon for the glycines of Gly-Xaa-Yaa repeats, and seven exons completely cover the NC11 domain. Comparison of the sequences encoded by these seven exons with the corresponding region of the alpha 1(XV) gene indicated conserved exon-intron organization, suggesting that the two genes derive from a common ancestor.