To reveal immunogenetic factors involved in the pathogenesis of metal allergy, 30 unrelated Japanese patients with histories of metal allergy were typed for HLA. They were confirmed by an unequivocal positive patch-test reaction to mercury, nickel or palladium. The HLA-DR and -DQ DNA were typed by using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSO) method. The frequency of each allele in the patient groups was compared to that in normal Japanese subjects. In mercury sensitive patients, there was no significant HLA association. In nickel sensitive patients, there was a significant increase of DRB4 (p < 0.05) but no significant association of DRB1 nor DQ locus, although there was an increase of DRB1*0405 (R.R = 2.36). In palladium sensitive patients, there were significant increases of DRB4 (R.R. = 15.48, p < 0.05), DR4(R.R. = 13.27, p < 0.005), DRB1*0405(R.R. = 4.43, p < 0.05), and DQB1*0401 (R.R. = 4.59, p < 0.05), and significant decreases of DRB5 (R.R. = 0.09, p < 0.05), and DQA1*0103 (R.R. = 0, p < 0.05).