We determined serum levels of type IV collagen 7S (IV 7S) in 73 (23 with normoalbuminuria, 21 with microalbuminuria, 17 with macroalbuminuria, and 12 primarily affected by nondiabetic renal disease (NDRD)) and 24 (10 with only macroangiopathy and 14 with retinopathy and macroangiopathy) diabetic patients to see whether IV 7S can be a useful index for differentiating early or overt diabetic nephropathy from NDRD in micro- or macroalbuminuric diabetics. IV 7S was significantly elevated in diabetic patients with micro-or macroalbuminuria compared to those with normoalbuminuria and healthy controls (p < 0.001). On the contrary, all 12 diabetic patients with micro- or macroalbuminuria due to NDRD showed normal or low IV 7S level. IV 7S was significantly higher in diabetic patients with both retinopathy and macroangiopathy than in those with only macroangiopathy (p < 0.001). We conclude that IV 7S levels may be a useful index to differentiate diabetic early or overt nephropathy from NDRD, especially nephrosclerosis, in micro- or macroalbuminuric diabetics.