Vascular complications are the main cause of morbidity in diabetes mellitus. However, the risk factors for vascular disease remain incompletely elucidated. It has been previously suggested that factors other than glycemia may contribute to the development of vasculopathy. In this study we determined the prevalence of phospholipid-binding antibodies in uncomplicated and complicated diabetes. We studied 53 uncomplicated diabetic patients, with type 1 (n = 32) or type 2 (n = 21) diabetes; 23 diabetic patients with proliferative retinopathy; 28 diabetic patients with an overt nephropathy; 37 diabetic patients with macroangiopathy and 22 non diabetic control patients. Both lupus anticoagulant and anticardiolipin antibodies were determined. Other risk factors for macroangiopathy were analysed. The prevalence of phospholipid-binding antibodies was similar in uncomplicated diabetic patients and in controls (type 1 diabetes: 9.4%; type 2 diabetes: 9.5%; control group: 4.6%; P= 0.76). In complicated diabetes, the frequency of these antibodies was increased only in patients with overt nephropathy (32.1%, P=0.01) or with macroangiopathy (32.4%, P=0.01) while patients with isolated retinopathy were comparable with uncomplicated diabetic patients (4.3%, P= 0.66). Uncomplicated diabetes was not associated with phospholipid-binding antibodies. We found a higher prevalence of these antibodies in diabetic patients with macroangiopathy or nephropathy. These results suggest a potential role of phospholipid-binding antibodies in the progression of vascular complications in diabetes mellitus.