Antineutrophil cytoplasmic antibodies (ANCA) are present in systemic vasculitis with or without renal involvement and in inflammatory bowel diseases, conditions which share damage in proteoglycan content of basal membrane. In diabetes, there is a reduction in proteoglycans in the kidney basal membrane, responsible for the decrease in fixed anionic charges and, consequently, for the prevalent anionic proteinuria (albumin, IgG4) even in the early preclinical stage of nephropathy. The aims of this study were to search for the presence of ANCA in long-standing type 1 diabetic patients and to evaluate possible correlations with size- and/or charge-selective proteinuria. Twenty-two type 1 diabetic patients (duration of diabetes 24 years, range 9-30) selected and grouped according to albumin excretion rate values, were studied together with 21 age and sex comparable normal subjects. ANCA, albumin excretion rate, and the clearances of albumin, of prevalently cationic total IgG (IgG) and of anionic IgG4 were evaluated. ANCA were measured using ELISA and indirect immunofluorescence methods; albumin, IgG and IgG4 were tested with RIA or ELISA methods developed in our laboratory. ANCA were found in five patients, three of whom showed proteinuria. 33.3% and 18.2% of patients with normal IgG and albumin clearances respectively had elevated IgG4 clearance. This study shows for the first time the presence of ANCA in long-standing type 1 diabetic patients and confirms a prevalent anionic protein excretion in these patients, but does not show a correlation between the presence of ANCA and proteinuria, even if the presence of ANCA in diseases sharing alterations in proteoglycan content of vascular basal membrane is noteworthy.