Psoriatic epidermis is characterised by a defective differentiation program leading to an abnormal permeability barrier and impaired desquamation. The corneodesmosin gene (CDSN) or "S" gene is a strong candidate in psoriasis susceptibility, due first to its genomic position ("S" gene, 160 kb telomeric to HLA-C) and second to its expression and function in the epidermis. Moreover, an association between CDSN and psoriasis vulgaris was recently shown in Caucasian populations. In order to pursue the CDSN polymorphism analysis, we determined the sequence of its alleles in 14 HLA-Cw6-positive individuals. A 4.6 kb genomic fragment encompassing the first exon, the unique intron and the coding sequence of the second exon was amplified from 8 psoriatic patients and 6 controls. Allelic discrimination was performed by restriction fragment length polymorphism analysis. The entire coding sequence and the intron boundaries of 27 alleles were sequenced. A total of 26 dimorphic sites were found, 23 consisting in single nucleotide polymorphisms (SNPs) and 3 in triplet modifications. Five out of the 23 SNPs have not been previously reported, and among them, one causes amino-acid exchange leading to the suppression of a potential chymotrypsin site. Among the triplet modifications, one leads to deletion of one out of five consecutive valines in the protein. The high polymorphism of the gene allowed the identification of 13 different alleles. These haplotypes will permit additional family-based studies that could provide new genetic support for the involvement of CDSN in psoriasis susceptibility. Moreover, the establishment of an extensive catalogue of CDSN alleles will allow functional analyses of the different protein isoforms.