Type V collagen is a minor represented and poorly characterized fibrillar collagen type. Previous cDNA cloning experiments showed that the amino-propeptide of the pro-alpha 2(V) chain shares structural features in common with pro-alpha 1(I), pro alpha 1(II) and pro-alpha 1(III) collagens. In the present paper, this analysis was extended to the gene level. Accordingly the exon/intron arrangement of the amino-propeptide coding domain was compared among pro-alpha 1(I) (COL1A1), pro alpha 1(II) (COL2A1), pro-alpha 1(III) (CO13A1) and pro-alpha 2(V) (COL5A2) collagen genes. This revealed that COL3A1 is the most closely related gene to COL5A2. Based on the assumption that critical regulatory elements might be phylogenetically conserved, we also compared the promoter sequences of the mouse and human COL5A2 genes. This revealed the highest level of sequence homology (97%) in a 52-bp segment which was previously shown to be essential in conferring cell type specificity to the human promoter.