Phosphorus (Pi) retention linked to chronic renal failure (CRF) favors secondary hyperparathyroidism (HPT). Reduction of Pi and protein intake has been shown to prevent the development of HPT in CRF. The aim of the present study was to assess in patients with advanced CRF the long-term effects on phosphate and calcium metabolism of a low-Pi (5-7 mg/kg/day), low-protein (0.4 g/kg/day) diet providing 300 mg/day calcium (Ca) and supplemented with amino acids and ketoacids, Ca carbonate (400-800 mg/day) and vitamin D<sub>2</sub> (1,000 IU/day). Twenty-nine patients with advanced CRF (glomerular filtration rate (GFR) 13.7 ± 4.5 ml/min) were selected for the study, on the basis of a follow-up of a least 2 years and a satisfactory compliance to the prescribed diet. At the start of the study, biological evidence of HPT was present with increased plasma PTH concentration (144 ± 95 pg/ml), increased plasma Pi (1.57 ± 0.33 mmol/l), an increase in alkaline phosphatase activity and plasma osteocalcin concentration. Plasma PTH concentration was positively correlated with plasma Pi and inversely with plasma Ca concentrations and GFR. Pi and protein restriction induced a significant correction of HPT within 3 months after starting the diet. After 2 years of diet, despite the diminution of GFR (11.1 ± 3.7 ml/min, p < 0.0001), plasma PTH was still lower than at the start of the diet (88 ± 57 pg/ml, p < 0.01), as was plasma Pi (1.32 ± 0.24 mmol/l, p < 0.001), total plasma Ca being higher (p < 0.01). Plasma PTH levels were correlated only to plasma Ca concentrations. However, variations in plasma PTH concentrations were correlated with changes in plasma Ca and Pi concentrations, but not with changes in GFR. Plasma calcitriol concentrations (measured in 14 patients) did not increase significantly. The results of the present study suggest that Pi and protein restriction with calcium supplementation and without calcitriol supplementation in patients with advanced CRF may induce a lasting correction of HPT, potentially mediated by the reduction of plasma Pi and the increase of plasma Ca concentrations, independently of plasma calcitriol.