BACKGROUND High dietary protein intake is a potential risk factor for nephrolithiasis because of its capacity to increase urinary calcium and to facilitate lithogenesis through many other mechanisms. OBJECTIVE Our aim was to verify the effects of moderate protein restriction in hypercalciuric patients. METHODS We studied 18 patients (10 men and 8 women aged 45.6+/-12.3 y) with idiopathic hypercalciuria and renal calculi. Before and after 15 d of a diet with 0.8 g protein x kg(-1) x d(-1) and 955 mg Ca, all patients were evaluated for the main serum and urinary measures of calcium metabolism as well as for urinary uric acid, oxalate, citrate, and prostaglandin E2. RESULTS Urinary excretion of urea fell after the diet (P < 0.001). Urinary calcium (P < 0.001), uric acid (P < 0.005), oxalate (P < 0.01), and hydroxyproline (P < 0.01) decreased after protein restriction, whereas urinary citrate increased (P < 0.025). Blood pH increased after the hypoproteic diet (P < 0.05). 1,25-Dihydroxycholecalciferol (calcitriol) concentration fell significantly (P < 0.025) and parathyroid hormone increased (P < 0.001). Creatinine clearance tended to decrease (106.4+/-4.8 compared with 97.5+/-5.7 mL/min) after the diet. The decrease in urinary uric acid after the diet correlated with calcitriol concentration (r = 0.57, P < 0.05) and the decrease in urinary urea correlated positively with that in hydroxyproline excretion (r = 0.58, P < 0.01). CONCLUSIONS In hypercalciuric patients, moderate protein restriction decreases calcium excretion, mainly through a reduction in bone resorption and renal calcium loss; both are likely due to a decreased exogenous acid load. Moreover, dietary protein restriction ameliorates the entire lithogenic profile in these patients.