Psoriasis is a chronic inflammatory skin disease with a strong genetic component. Linkage studies have identified several susceptibility loci for psoriasis including a region on chromosome 1q21 termed the 'epidermal differentiation complex'. At least 20 genes involved in epidermal differentiation and proliferation have been mapped to this region including S100A2, a gene known to be over-expressed in psoriasis lesions. In the course of cloning and sequencing several S100A2 cDNAs, we identified an A/G (Asn62Ser) polymorphism at nucleotide 185 of the S100A2 coding region. To determine whether this polymorphism is associated with psoriasis, we tested DNA from 38 unrelated normal and 40 unrelated psoriatic individuals. The 185G allele was present in 148 of the 156 chromosomes analysed, giving an allele frequency of 94.9%. All of the remaining chromosomes carried 185A. There was no significant difference in the allele distribution between normal and psoriatic individuals (normals 72G, 4A; psoriatics 76G, 4A; P = 1.00 by Fisher's exact test). Our data explain conflicting results in the literature regarding the sequence of S100A2 but provide no support for a direct causal role for S100A2 in psoriasis.