1. We examined the effects of various levels of dietary protein on the course of adriamycin-induced nephropathy in rats fed with high (30%), intermediately low (10%) or strictly low (5%) protein diets for 24 weeks.
2. In the rats fed on the 30% protein diets, there were massive proteinuria, progressive increases in serum creatinine and focal glomerular sclerosis associated with severe tubulo-interstitial changes.
3. With the 5% dietary protein, proteinuria was decreased, the levels of serum creatinine were preserved within normal ranges and renal histological changes diminished. Weight loss and hypoproteinaemia were more marked.
4. With intermediate protein restriction (10% protein), renal function and plasma protein were preserved but body weight did not increase normally.
5. Aggregated human immunoglobulin G, which had been intravenously injected at weeks 12 and 24, accumulated in the glomeruli more densely in rats fed on the 30% protein diet than in those fed on the 10% or 5% protein diets.
6. We tentatively conclude that functional and histological deterioration of focal glomerular sclerosis can be prevented by appropriate restriction of dietary protein; however, severe protein restriction does aggravate nutritional states.