Comparative analysis of renal biopsy findings and clinical status in patients with different types of glomerulopathy (primary glomerulonephritis, 1747; diabetic glomerulosclerosis, 488; renal AA and AL amyloidosis, 225) was undertaken to investigate the pathogenesis of chronic renal failure in these diseases. Morphometric, cytological and electron-microscopic investigations were undertaken and yielded the following results: 1. Disease of the renal corpuscles alone, even if it is very severe, does not lead to renal insufficiency or even elevation of the serum creatinine concentration. 2. Chronic renal insufficiency develops only in those cases of glomerulopathy in which the postglomerular capillaries in the renal cortex exhibit chronic inflammation that causes such severe narrowing of these vessels as to impair glomerular perfusion. 3. The passage of basement membrane material from the glomerular capillaries into the primary urine may play a critical role in the pathogenesis of some forms of chronic renal failure, since this material can be reabsorbed by the tubules and is probably presented as an autoantigen to intraepithelial T lymphocytes by proximal tubular epithelial cells that express distinct HLA class II antigens and ICAM-1. 4. The presentation of these autoantigens to intraepithelial T lymphocytes leads in genetically predisposed individuals to an autoimmune response with a consequent marked increase in numbers of T lymphocytes and an increase in macrophages/monocytes, fibroblasts/fibrocytes and plasma cells, and increased production of extracellular matrix by fibroblasts/fibrocytes. 5. The increase in extracellular matrix leads to obliteration of the postglomerular capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)