Fibromyalgia syndrome (FS) is a frequently seen extra-articular rheumatism of unknown etiology. Some authors have suggested a direct role of the immune system in the pathogenesis of the disease while others have found an increased prevalence of some HLA DR and B antigens. The aim of our study was to verify the possible association between HLA and FS in Italian patients with no clinical or immunological evidence of chronic rheumatic inflammatory diseases. Ninety-two consecutive Italian patients were evaluated: 86 were typed for HLA A-B-C antigens and 74 for HLA DR antigens. The study was performed by standard NIH microlymphocytotoxicity technique and by NIH prolonged technique on B lymphocyte purified preparations. There was no statistically significant difference between any HLA A-B-C and DR antigens in the patients compared with the controls. We conclude that in the pathogenesis of FS there is no clear cut evidence of immunologic or genetic involvement.