To establish the relation between HLA antigens, Primary Sjögren Syndrome (PSS) and autoantibodies production, in our geographical area, we undertook a case-control study with a consecutive sample of 30 patients with PSS (Fox's criteria) attending in a reference hospital. Two hundred and sixty-four local controls with no apparent pathology were included for comparison. In patients we evaluated clinical and analytical aspects about multisystem autoimmune disease. Anti-SSA/Ro and -SSB/La autoantibodies were determined by double immunodiffusion. HLA typing was serologically determined. In logistic regression multivariate analysis, there were significant association between PSS and specificities HLA-Cw7 (73% in cases, versus 35% in controls; RR = 8.0; 95% CI: 23.2-2.7), HLA-DR3 (63% vs 20%; RR = 3.4; 95% CI: 9.5-1.4) and HL-DR11 (43% vs 13%; RR = 4.1; 95% CI: 12.0-1.4). In patients, the anti-SSA/Ro autoantibodies production were associated with HLA-DR3 antigen (83% vs 25%; RR = 6./; 95% CI: 1.3-34.2). All HLA-DQ2/DQ6 heterozygotes patients (8 cases) had anti-SSA/Ro autoantibodies, versus only one half of the remainder (p = 0.029; RR = 6.3). In anti-SSA/Ro negative patients there weren't association with HLA-DR3 antigen (33% vs 20%). HLA-DR3 were associated with the presence of anti-SSB/La autoantibodies, but there wasn't signification (p = 0.081). We conclude that our patients with PSS present association with HLA-DR11 specificity, that it's a risk factor for the disease development. HLA-DR3 would determined the anti-SSA/Ro autoantibodies, and maybe also anti-SSB/La autoantibodies, production. Furthermore, HLA-DQ2/DQ6 heterozygosity would determined immune response to SSA/Ro autoantigen.