Twenty chronically azotemic patients (experimental group) with a mean creatinine clearance of 22.5 +/- 9.4 ml/min followed a diet supplying daily, per kilogram of body weight, 7.0 mg of phosphorus and 0.5 g of protein, mostly of high biological value, for 11.3 months. A group of 19 similar patients (control group) followed a diet supplying daily, per kilogram of body weight, 12 mg of phosphorus and 0.8 g of protein for a similar period of time. In the experimental group, the serum inorganic phosphorus, urea, and iPTH (both N-terminal and C-terminal fragments) decreased significantly. The creatinine clearance decreased by -0.59 +/- 0.7 ml/min per month prior to the commencement of the experimental diet and increased by a mean of 0.1 +/- 0.4 ml/min per month during the period of study. In the control group, the serum inorganic phosphorus increased, the serum urea and iPTH remained practically constant, and the mean creatinine clearance continued to decrease at a rate not significantly different from that prior to the onset of the study (-0.50 +/- 0.66 and -0.44 +/- 0.10 ml/min per month, respectively). The mechanisms by which the low-phosphorus, low-nitrogen diet slows the progression of renal failure are discussed, and the practical importance of prescribing the dietetic restriction early in the course of renal disease is stressed.