The association of specific HLA-C nucleotide sequences with psoriasis vulgaris was investigated in 75 Japanese patients by the polymerase chain reaction method, followed by slot-blot hybridization using two specific oligonucleotide probes. The synthesized nucleotide primers were C180P, 5'-GACCGGGAGACACAGAAGTACAAG-3' (coding for amino acid residues 61 to 68 of the alpha 1 domain of the HLA-C molecule) and C243PR, 5'-GCTCTGGTTGTAGTAGCCGCG-3' (residues 82 to 88), respectively. The amplified sequence detected with the probe C208A (5'-AGGCACAGGCTGACCGA-3'), including the coding region for alanine at position 73, was significantly increased in frequency in the patients compared with the healthy individuals (81% versus 48%, relative risk = 4.7, chi 2 = 15.3, p less than 0.0001). This specific nucleotide sequence is common to Cw6 and Cw7, but some other HLA-C alleles including Cw4 and C blank (Cx52) also proved to have this sequence. It is suggested that alanine at position 73 of HLA-C molecules can be a good marker for psoriasis vulgaris and that this residue may play an important role in determining susceptibility to this disease.