We isolated full-length cDNA clones for human matrilin-2, an oligomeric protein, which forms filamentous networks in the extracellular matrices of various tissues. The human matrilin-2 precursor is encoded by a 4.0-kb mRNA, it consists of 956 amino acids and shows 93% similarity to the mouse protein. Out of the two von Willebrand factor type A-like domains, the 10 epidermal growth factor-type modules, one unique sequence and the oligomerisation module, the first A domain is the most conserved. RT-PCR demonstrated wide expression of the gene in human cell lines of fibroblastic or epithelial origin. Alternative splicing affected only 19 amino acids in a 75-moiety-long segment, unique to matrilin-2. Isolation and analysis of the 3′ end of the gene revealed that the reason for alternative splicing is alternative 3′ splice site selection. Further, we identified in the human matrilin-2 gene a U12 type AT–AC intron between the last two exons encoding the oligomerisation domain. We mapped the matrilin-2 gene (MATN2) by fluorescence in situhybridization at chromosome position 8q22.