Different distributions of segmental lesions within glomeruli correspond to different pathogenetic mechanisms. A graphic method of analysis of the position of segmental lesions was applied to 106 Kimmelstiel-Wilson nodules in 10 renal biopsies from patients with diabetic glomerulonephropathy, 4 with IDDM and 6 with NIDDM. The nodules were randomly distributed in a horseshoe-shaped area corresponding to the peripheral or intralobular mesangium. This distribution was different from that of segmental lesions studied previously in the glomerular tip lesion, in vasculitic-type glomerulonephritis, and in hyperfiltration associated with reduced renal mass. Our finding is consistent with ideas that Kimmelstiel-Wilson nodules have a distinct pathogenesis not related to hyperfiltration or any other process previously investigated as a cause of characteristic distribution of segmental lesions.