A relationship between the presence of platelet autoantibodies and major histocompatibilty complex class II alleles was determined in 27 patients with lupus anticoagulants. Twenty-two patients had a primary antiphospholipid syndrome' and five patients had lupus erythematosus (SLE). Platelet antibodies against the platelet glycoproteins (GP) IIb/IIIa were detectable in 20 patients. Anti-GPIb/IX or -GPIV antibodies were detectable only in patients with anti-GPIIb/IIIa antibodies. An increased frequency of HLA-DQB1*06 was demonstrable in the total patient population. The association between the lupus anticoagulants and HLA-DQB1*06 was even stronger if patients also had detectable platelet antibodies. This association was also seen if patients with a history of thromboembolic disease were considered separately. However, within the patient population there was no difference between frequencies of HLA alleles detectable platelet antibodies.