FAJARDO, L. F., BROWN, J. M., AND GLATSTEIN, E. Glomerular and Juxta-glomerular Lesions in Radiation Nephropathy. Radiat. Res. 68, 177-183 (1976). Endothelial cell damage progressing to extensive thrombosis of glomerular capillaries has been observed 1 to 12 months after fractionated, in situ X irradiation of murine kidneys with total doses ranging from 3000 to 5000 rad. These changes support the concept that radiation injures primarily glomeruli in mice. Because of the morphologic similarities (by light microscopy) between murine and human late lesions, it is likely that glomerular endothelial cell damage, and subsequent thrombosis, also occurs in humans. Unexpected alterations were found, again by electron microscopy, in the juxta-glomerular apparatus: the epithelioid cell granules often showed vacuolation, and osmiophilic deposits, as well as formation of large electron-dense crystals. These lesions in the juxta-glomerular granules may be related to radiation, to hypertension, or to both. Although the clinical characteristics of human radiation-induced renal disease have been well described (1), its pathogenesis and the initial site of radiation injury in the kidney are not clearly established. Likewise, there is no satisfactory explanation for the arterial hypertension, which occurs in most patients. The initial site of radiation injury in mammalian kidneys is in dispute. Investigators working with rats have suggested that small arteries may be initially damaged and that the rest of the renal parenchyma suffers secondarily, probably as the result of ischemia (2, 3). From other experiments in dogs and mice, it has been suspected that epithelial tubular cells bear the initial damage (4, 5). Some investigators have been impressed by the early appearance of glomerular lesions, and have indicated that glomeruli may be primarily injured (perhaps simultaneously with tubules) (6-9). These conflicting results are partially explained by variation in the response from one animal species to another. This variation is shown in an extensive review of the subject by Mostofi and Berdjis (10). The pathologic material available from humans usually shows end-stage renal disease in which the initial damage can no longer be recognized. Nevertheless, even in these late-stage specimens from our material (9) or from that of others, we have been impressed by the preponderance of glomerular lesions and the paucity-and often absence-of detectable arteriolar damage. Renal samples