Types XV and XVIII collagens form a new subgroup within the diverse family of collagens, both being characterized by extensive interruptions in their collagenous sequences. We isolated human alpha 1(XV) chain cDNAs that extend beyond the sequences previously derived from a 2127-nucleotide clone. The cDNAs cover 5172 nucleotides of the 5300-4400-nucleotide mRNAs and encode a polypeptide of 1388 residues, including a 25-residue signal peptide, a 530-residue NH2-terminal noncollagenous domain (NC1), a 577-residue collagenous sequence with eight interruptions of 7-45 residues, and a 256-residue COOH-terminal noncollagenous domain (NC10). A thrombospondin sequence motif found previously in certain other collagen types was identified in the NC1 domain of type XV collagen, whereas the NC10 domain was characterized by the presence of four cysteine residues. The exon-intron organization of the human gene was determined, corresponding to the extreme COOH-terminal 2/3 + 275 residues. NC10 is encoded by seven exons, six of which encode solely protein sequences and vary in size between 60 and 186 base pairs, whereas the last one corresponds to the end of the polypeptide and the 3'-untranslated sequences. The extreme 5' exon analyzed was a junction exon encoding both collagenous and noncollagenous sequences. This initial characterization is indicative of a multiexon arrangement for the alpha 1(XV) gene.