Diabetic nephropathy is characterized by an early period of renal growth with glomerular and tubular cell hypertrophy, but this is followed by progressive glomerulosclerosis and tubulointerstitial fibrosis, associated with loss of renal tissue. We studied whether apoptotic cell death occurs in human diabetic nephropathy. Percutaneous renal biopsy samples were obtained from five patients with diabetic nephropathy who were receiving insulin and/or angiotensin-converting enzyme inhibitor therapy. Apoptosis was determined by the presence of DNA fragmentation, detected by in situ TUNEL staining, and by characteristic features on electron microscopy, such as chromatin condensation. Apoptosis was present in all five biopsy specimens, either in epithelial cells of the proximal or distal tubules, or in endothelial cells or interstitial cells. No apoptosis was detected in cells of the glomeruli. The present study provides evidence for apoptosis in human diabetic kidney, and suggests a role for apoptosis in the gradual loss of renal mass.