Objective: The aim of this study was to investigate association between systemic lupus erythematosus (SLE) and HLA antigens in Caucasoid Brazilian population. Methods: The HLA-A, B, DR and DQ antigens typing was performed using microlymphocytotoxicity test. Fifty-six unrelated Brazilian Caucasoid patients with SLE were studied. Control population for HLA A and B antigen frequency consisted of one hundred-fifty nine unrelated healthy Brazilian Caucasoid and for HLA DR and DQ one hundred-forty one. SLE patients were divided in two groups: 1) with nephritis and 2) without renal involvement. Results: The frequency of HLA-B8 was significantly increased in SLE patients than in controls (25.4% vs 6.9%). HLA-DR2 was significantly increased in SLE patients than was in controls (41% vs 19.1%, RR = 2.95; p < 0.005). When SLE nephritis patients were compared to controls, the frequency of HLA-DR2 (44% vs 19.1%) and HLA-DR3 (32% vs 14.2%) were significantly increased. On the other hand, the frequency of HLA-DR2 was increased in the group of SLE patients without renal disease when compared with control group (37.5% vs 19.1%). Conclusion: Our data suggested that HLA-B8 and HLA-DR2 might have a role in the susceptibility to SLE and HLA-DR3 may be associated with nephritis in Caucasoid Brazilian population with SLE.38633233