We have isolated overlapping mouse cDNAs encoding a collagenous polypeptide that we have designated alpha 1(XVIII) collagen. Nucleotide sequence analysis shows that alpha 1(XVIII) collagen contains 10 triple-helical domains separated and flanked by non-triple-helical regions. Within the non-triple-helical regions, there are several Ser-Gly-containing sequences that conform to consensus sequences for glycosaminoglycan attachment sites in proteoglycan core proteins. Northern blots show that alpha 1(XVIII) transcripts are present in multiple organs, with the highest levels in liver, lung, and kidney. We have also isolated overlapping cDNAs encoding human alpha 1(XV) collagen, and their sequence extends a published partial alpha 1(XV) sequence to the 3' end. Comparison of the alpha 1(XV) and alpha 1(XVIII) sequences reveals a striking similarity in the lengths of the six most carboxyl-terminal triple-helical domains. In addition, within the carboxyl non-triple-helical domain NC1 of the two chains, a region of 177 amino acid residues shows about 60% identity at the amino acid level. We suggest, therefore, that alpha 1(XV) and alpha 1(XVIII) collagens are structurally related. Their structure is different from that of other known collagen types. We conclude that they belong to a subfamily of extracellular matrix proteins and we suggest the designation multiplexins (for protein with multiple triple-helix domains and interruptions) for members of this subfamily.