Healthy adult dogs were subjected to stepwise reduction of nephron population so as to create the transition from normal renal function to advanced renal insufficiency. Studies were performed at each level of renal function. Glomerular filtration rate (GFR), renal phosphate clearance, and serum radioimmunoassayable parathyroid hormone (PTH) levels were measured. Two groups of animals were studied. In one, phosphorous intake was maintained at 1200 mg/day. As GFR declined, fractional phosphate excretion rose reciprocally, and PTH levels increased over 20-fold. In the second group, phosphorous intake was maintained at less than 100 mg/day. As GFR fell, fractional phosphate excretion changed little, and no increment in PTH levels occurred. The data suggest that the control system regulating phosphate excretion contributes importantly to the pathogenesis of secondary hyperparathyroidism in advancing renal insufficiency.