Susceptibility to and outcome for rheumatoid arthritis (RA) have been associated with particular HLA-DR alleles, but these alleles vary among ethnic groups and geographic areas. The frequency of HLA-DR1 (HLA-DRB1*0101, DRB1*0102) and HLA-DR4 (DRB1*0401, DRB1*0404) alleles is elevated among Caucasian patients with RA. We studied a northeastern Hungarian population of RA patients to determine the frequency of HLA-DR1 and HLA-DR4 phenotypes in this population and to compare it with healthy control subjects, as well as to investigate whether the presence of these alleles could be a marker for RA. We performed HLA-DRB1 genotyping (DRB1*01-DRB1*16) in 83 RA patients and 55 healthy controls using polymerase chain reaction with sequence-specific primers (PCR-SSP). In the case of HLA-DR1- or HLA-DR4-positive patients, the DR1 and DR4 subtypes were also determined. The frequency of HLA-DR4 alleles was significantly higher in RA patients than in controls (31.3 vs. 10.9%; P <.05). HLA-DR1, in particular, tended to be more frequent in patients than in controls (32.5 vs. 18.1%). Among the HLA-DR4 subtypes, DRB1*0401 and DRB1*0404 were the most common alleles found in both groups. However, no significant differences were seen in the frequency of HLA-DRB1*0401 and HLA-DRB1*0404 between RA patients and controls. In contrast, HLA-DRB1*0405 and HLA-DRB1*0408 were significantly more common in RA patients than in control subjects. Among HLA-DR1 subtypes, the DRB1*0101 allele was most commonly detected, but HLA-DRB1*0101 as well as DRB1*0102 and DRB1*0105 were similarly frequent in RA patients and controls. HLA-DR12 was more common among controls than in RA patients (18.1 vs. 0%; P <.05). Our results generally agree with the findings in other Caucasian populations. Nonetheless, we found differences in the frequency of HLA-DR1 and HLA-DR4 subtypes among Hungarian patients compared with reports from other geographic regions (e.g., Finland and Asia). Our data suggest that in northeastern Hungary, HLA-DR4 as well as its subtypes DRB1*0405 and DRB1*0408 may be involved in susceptibility to RA, but HLA-DR1 may not. In addition, the presence of HLA-DR12, at least in Hungary, may protect from this disease.