Increased morbidity and mortality occur in diabetics with kidney disease. The decrease in fixed anionic charges is considered an early abnormality occurring well before any clinical sign of disease. It has been attached importance to the study of protein charge-selectivity decreased in diabetes in order to find the parameters which highlight the initial preclinical stage of diabetic nephropathy. To investigate the role of protein charge in early diabetic proteinuria, the clearance of protein differing in charge and/or size (anionic and cationic IgG, albumin) was evaluated in type 1 diabetic patients: 18% of them showed increased values of albuminuria. Anionic and total IgG clearances significantly increased in 30% and 12% of the patients and were correlated with the duration of the disease. The anionic/cationic IgG clearance ratio tended to increase in parallel with albumin clearance, but once above macroalbumonuric levels, it tended to fall again, indicating the concomitant presence of size-selectivity loss. In addition to albumin excretion, the anionic IgG clearance and the anionic/cationic IgG ratio, may be valuable in assessing early kidney protein charge-selectivity impairment and in better characterizing normoalbuminuric patients and those in the preclinical stage of diabetic nephropathy.