Abstract:We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) genes: HLA‐DRB, ‐DQA, ‐DQB, ‐DPB in 24 Danish patients with systemic lupus erythematosus (SLE) and in 102 healthy Danes. A highly significant increase of the frequency of the DR3‐ and DRw6‐associated 7.00 kb DRBTaqI DNA fragment was found in SLE patients compared to normal controls (83.3% vs 35.5%; RR = 9.1, p<10‐4). The frequencies of the DQA1*0501‐associated 4.56 kb DQATaqI fragment and the DRB3*01/03‐associated 9.79 kbTaqI fragment were also found to be significantly increased in SLE patients (70.8% vs 29.7%; RR = 5.8, p<10‐2for the DQA fragment and 70.8% vs 36.1%; RR = 4.3, p<0.05 for the DRB3 fragment). Less extensive and insignificant increases of the frequencies of the DR3‐associated DQB and DPB fragments were observed. The frequencies of the DR2‐associated DRB, DQA, and DQB fragments were comparable to those f