The effect of 20 Gy intraoperative bilateral local kidney irradiation was compared in rats treated after irradiation with dexamethasone and untreated rats. Ninety days after irradiation, body weights, WBC, RBC, hematocrit, and renal function (plasma urea nitrogen concentration and retention of ethylene- diaminetetraacetic acid) were measured. The animals were then sacrificed and the kidneys were analyzed for water and hydroxyproline content and examined histologically. Local kidney irradiation reduced animal growth, prevented renal growth, decreased renal mass and renal function, and increased the water and hydroxyproline content of the kidneys. Histopathological examination revealed glomerular damage (atrophy, decreased RBC and endothelial cells, increased mesangial matrix), tubular damage (epithelial denudation, congestion with hyalin casts), and increased concentration of interstitial cells. Dexamethasone treatment significantly ameliorated the effects of kidney irradiation on body weights, renal mass, renal function, and the development of anemia. Dexamethasone had no effect on radiation- induced edema or fibrosis as measured by the water and hydroxyproline content of the kidneys. Dexamethasone-treated irradiated kidneys had significantly less damage to the glomeruli and tubules. The results suggest that dexamethasone is cytoprotective and prevents the destruction of the nephron.