Phosphorus retention as a result of chronic renal failure (CRF) induces secondary hyperparathyroidism (HPT II) while supplemented low-phosphorus low-protein diets (LPD) prevent it. The aim of this study was to assess in seven patients with advanced CRF and biological HPT II the effects of a LPD providing daily 5 to 7 mg/kg phosphorus, 0.4 g/kg protein, 300 mg calcium (Ca) and supplemented with amino acids, ketoacids, CaCO3 and vitamin D2, on the relationship between ionized Ca (iCa) and PTH concentrations. Hyper- and hypocalcemia were induced by CaCl2 and Na2-EDTA infusion. After three months of LPD, serum phosphorus decreased from 1.59 +/- 0.15 to 1.26 +/- 0.24 mmol/liter (mean +/- SEM, P < 0.02), basal PTH levels from 251 +/- 25 to 127 +/- 16 pg/ml (P < 0.03), while basal iCa and GFR did not vary. The sigmoidal PTH-calcium curve shifted downward with maximal PTH decreased from 482 +/- 86 to 319 +/- 60 pg/ml (P < 0.02) and minimal PTH from 35 +/- 4 to 21 +/- 4 pg/ml (P < 0.05). On the other hand, the slope of the % maximal PTH-iCa curve, which is an indicator of the sensitivity of the parathyroid cell to changes in iCa concentrations, did not vary significantly. The set point of Ca and calcitriol levels were not modified. These results demonstrate a direct inhibition of PTH secretion over a wide range of iCa concentration by LPD in patients with advanced CRF and mild HPT II over a three months period. This effect is independent of changes in plasma calcitriol levels.