Abnormalities of the central nervous system (CNS), as discerned by neuroelectrophysiological studies, and an impaired, charge-related, differential filtration of protein at kidney level as evaluated by selective protein clearance, have recently been shown in diabetes of short duration and without any apparent complication. In order to explore the time of appearance and possible correlations, CNS and kidney abnormalities have been evaluated in parallel both in short-term and long-standing type 1 diabetic subjects. Two groups of patients were studied: Group 1 (no. 15), with no previously known clinical sign of complications and less than 5 years from diagnosis; Group 2 (no. 15) with more than 10 years of disease and with or without clinical signs of diabetic complications. Twenty age and sex comparable normal subjects were included in the study (Group 3). Short-latency multimodal evoked potentials (visual-VEP, brainstem auditory-BAEP, median and tibial somatosensory m- and t-SEP) and charge and/or size selective protein clearances (albumin, anionic immunoglobulins, neutral/cationic immunoglobulins) were evaluated. In Group 1, 27% of patients showed neurophysiological abnormalities (P < 0.05 vs. Group 3) while one showed proteinuria. In Group 2, 60% of patients showed electrophysiological changes (P < 0.0001 vs. Group 3) while 67% showed abnormal charge or size selective proteinuria (P < 0.0001 vs. controls) with a significant association between the abnormalities of CNS and of charge selective proteinuria (P < 0.05). Thus, CNS abnormalities may be detected even in patients with diabetes of short duration and are later associated with subclinical kidney abnormalities. These findings stress the value of the multimodal evoked potential evaluation as a sensitive and early diagnostic approach to the study of diabetic complications.