The presence of anti-phospholipid antibodies (aPL) has been associated with the major histocompatibility complex (MHC) genes. These autoantibodies occur in individuals with infections such as that produced by the human immunodeficiency virus 1 (HIV-1) or with syphilis, but they can also occur in drug-induced lupus-like syndromes. In the present study, we analysed the presence of aPL (detected as lupus anti-coagulant) and its relationship with the MHC markers in 93 Caucasian psychiatric patients chronically treated with chlorpromazine. Forty-one out of 93 patients were positive for LA, and the HLA-DR7 antigen was significantly increased in LA-positive patients as compared to normal controls or LA-negative patients (PC = 0.024, RR = 2.12 and P = 0.05, RR = 1.57, respectively). Likewise, we noted a significantly increased frequency of HLA-B44 in LA-positive patients as compared to normal controls (PC = 0.024, RR = 2.12), but not when compared to aPL-negative patients. No significant differences were found among any other class I, II or III MHC antigens. Haplotype analysis showed that DR7 was mostly part of the HLA-B44-DR7-FC31 and B7-DR7-SC31 haplotypes. These results suggest that the HLA-DR7 antigen might be playing a role in the production of aPL in chlorpromazine-treated patients.