We investigated the association of HLA-DPB1 alleles with the occurrence of autoantibodies against Ro (SS-A) or La (SS-B) using recombinant 52 kD-Ro, 60 kD-Ro and La proteins in 177 German patients with systemic lupus erythematosus (SLE). A significant increase in the frequency of DPB1*0101 is observed in SLE patients compared to healthy controls (Pcorr.. < 0.004). Antibodies against 52 kD-Ro, 60 kD-Ro and La are tested by ELISA and are found with a frequency of 25.4%, 33.9% and 17.5% in the patients, respectively. An association with HLA-DPB1*0101 is observed for antibodies against La (P < 0.01) and 52 kD-Ro (P < 0.01), but not for 60 kD-Ro in the absence of La/52 kD-Ro. Since there is a strong linkage disequilibrium between DPB1*0101 and DR3 in the normal population and in SLE patients, and since there is an association between DR3 and SLE, as well as between DR3 and the occurrence of recombinant Ro/La antibodies in SLE patients, we investigated whether DPB1*0101 is associated per se or via linkage disequilibrium with DR3. DPB1*0101 in the absence of DR3 is not more common in patients than in controls and not in patients with autoantibodies to Ro and La than without autoantibodies. We conclude that there is no evidence for a direct involvement of DPB1*0101 in the production of Ro/La autoantibodies in SLE patients.