To investigate selective protein permeability in early diabetic glomerulopathy, urinary total IgG and IgG4 excretion and urinary albumin excretion were compared in patients with non insulin-dependent diabetes mellitus (NIDDM). Sixty one NIDDM patients were classified according to their albumin excretion rate (AER) determined on the basis of overnight urine collections (22: AER<20μg/min, normoalbuminuria; 21: AER 20 to 200μg/min, microalbuminurla; 18: AER>200 μg/mnin, macroalbuminuria) NIDDM patients and 36 normal controls were analyzed for urinary total IgG, IgG4 and urinary NAG excretion. Urinary total IgG was detected by novel non-immunological competitive assay (biotin-avidin method), and IgG4 was detected using a newly developed ELISA employing anti-IgG4 monoclonal antibody. U-Total IgG levels were significantly higher in both microalbuminuria and macroalbuminuria in comparison with normoalbuminuria or controls (p<0.01 and p<0.05, respectively). U-IgG4 levels were significantly increased in both macroalbuminuria and microalbuminuria, compared with normoalbuminuria and the controls (p<0.05). U-total IgG levels were clearly elevated in normoalbuminuria compared with the controls (p<0.01), whereas U-IgG4 levels for normoalbuminuria were within the normal range. Urinary NAG excretion was similar in the controls and the other groups. These data indicate that selective urinary excretion of different IgG subclasses appears to provide a method of assessing besement membrane impairment in early diabetic nephropathy and may serve as an additional parameter to precisely characterize incipient diabetic nephropathy.