Chronic effects of dietary protein in the rat with intact and reduced renal mass. The chronic effects of dietary protein on renal structure and function were studied in rats with normal and reduced renal mass. Control rats with two kidneys were compared with unilaterally nephrectomized rats, and with one and one–third nephrectomized rats obtained by unilateral nephrectomy and infarction of one–third of the remaining kidney. Rats at each level of renal mass were maintained on chow containing either 6% or 40% protein content. Separate cohorts of rats were studied four and eight months after ablation and institution of these dietary regimens. At both time intervals and at all levels of renal mass, rats fed the high protein diet had higher average values for GFR than comparable animals fed the low protein chow. Within each of the dietary regimens the animals with loss of renal mass developed greater prevalences of sclerotic glomeruli by eight months. Furthermore, at each level of initial renal mass, rats eating the high protein diet had a greater prevalence of sclerotic glomeruli than those on the low protein diet. Similarly, rats on the high protein diet had greater rates of protein excretion than those on the low protein diet at each degree of ablation. The prevalence of sclerosed glomeruli increased between four and eight months in each group. Thus, the extent of renal injury as manifested by proteinuria and glomerular sclerosis was directly related to the degree of initial loss of renal mass, and dietary protein restriction retarded these manifestations of injury across a wide range of initial renal mass. These chronic observations are in accord with the hypothesis that substantial glomerular hyperfiltration and hyperperfusion eventuate in progressive glomerular injury, and support the view that dietary protein restriction in the setting of reduced renal mass can afford considerable long–term protection of the glomerulus.