We examined the effects of dietary protein restriction in fourteen patients with chronic kidney rejection. The patients were randomly assigned, using a crossover design to two 11-day periods, one on a low-protein diet (0.55 g/kg/day) and the other on a high-protein diet (2 g/kg/day). The low protein diet was associated with a significant improvement in glomerular permselectivity without any change in blood pressure, glomerular filtration rate, or renal plasma flow. The low protein diet was also associated with a significant reduction in plasma renin activity. Acute converting enzyme inhibition decreased proteinuria when administered at the end of the high protein diet, but had no additional antiproteinuric effect when given at the end of the low protein diet. Comparable reductions in blood pressure with hydralazine had no effect on proteinuria. Protein restriction was also associated with modest but significant fall in serum proteins. In conclusion, dietary protein restriction may improve the course of renal failure in chronic rejection partly by suppressing the renin-angiotensin system. Studies are needed to establish the safe level of dietary protein restriction in these patients and to assess the efficacy of such restriction in slowing the progression of renal failure.