Previous HLA serological studies showed positive associations of the DR52 antigen, the DR52-associated antigens (DR3, DR5 and DR6) and the DR8 antigen with sarcoidosis. To investigate the HLA alleles that may contribute to the genetic susceptibility to sarcoidosis at the DNA level, HLA-DRB1, -DRB3, -DQA1 and DQB1 genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed in 63 Japanese patients with sarcoidosis. The frequencies of the DR52-associated DRB1 alleles (DRB1*11, DRB1*12 and DRB1*14 except DRB1*1302), DRB1*08, DRB3*0101, DQA1*0501 and DQB1*0301 were significantly increased in patients compared with healthy controls. The significant increase of DRB3*0101, DQA1*0501 and DQB1*0301 could be explained by linkage disequilibrium with the DR52-associated DRB1 alleles. It must be noted that the DR8 haplotype, which does not possess the DRB3 gene, also showed a significant increase in sarcoidosis. These results suggest that the HLA-alleles responsible for the susceptibility to sarcoidosis are located at the HLA-DRB1 locus rather than the HLA-DRB3, -DQA1 and -DQB1 loci. In contrast, DRB1*1302 may confer resistance to the disease.