Scanning electron microscopy (SEMy), supplemented with light microscopy and transmission electron microscopy, was used to study aminonucleoside nephrosis in rats. The visceral epithelium undergoes dramatic restructing in response to aminonucleoside nephrosis. Due in part to an accumulation of intracellular vacuoles, kidney podocytes swell in size. Podocyte major processes lose their many pedicles and slit pores and form close junctions (80 A) with adjacent podocytes. Although no prominant pores opening into the urinary space are found in the visceral epithelium, there is evidence that podocyte vacuoles may rupture and thereby release protein into the urinary space. Many parietal cells also increase in size, accumulate intracellular vacuoles and come into very cose proximity to the visceral epithelium. Casts of PAS-positive, electron-dense material fill the lumina of many uriniferous tubules. Although most proximal tubules exhibit an extensive loss of brush border, no significant changes in other kidney microprojections or cilia were noted. Transmission electron and light microscopy of nephrotic kidneys reveal considerable changes in proximal and distal tubules including a reduction in mitochondria, in cell height, in electron density of the cytoplasmic matrix, in lateral and basal plasmalemma infolds, enlarged euchromatic nuclei, dilated lumens, and accumulation of PAS-positive cytoplasmic granules. SEMy of kidney needle biopsies from patients with proteinuria reveal that SEMy is useful for evaluating glomerular changes in man.