We have examined the effects of various levels of dietary protein intake on the course of nephrotoxic serum nephritis in the rat by feeding low (4.6% casein), standard (23% casein), and high (57.5% casein) protein diets which were identical in calorie, mineral, and electrolyte content. Nephritic rats on a high protein diet manifested heavy proteinuria, hypoalbuminemia, hypercholesterolemia, azotemia, and elevated serum creatinine levels. In those subjected to dietary protein restriction, proteinuria remitted and azotemia did not develop. While mesangial widening, interstitial abnormalities, and segmental proliferation and sclerosis of glomeruli occurred regularly in nephritic rats fed high protein diets, histologic abnormalities were virtually absent in those on low protein intake. Animals on a standard protein intake manifested histologic and clinical features intermediate in severity. We conclude that the renal functional and histologic consequences of nephrotoxic serum nephritis can be averted by dietary protein restriction.