The effect of citrus fruit juice ingestion on the risk of calcium oxalate stone formation is still debated. The present study was undertaken to investigate changes in urinary stone risk factors after administration of a soft drink containing grapefruit juice. Seven healthy subjects, with no history of kidney stones, were submitted to an acute oral load (20 ml/kg body weight over 60 min) of a soft drink containing grapefruit juice diluted (10%) in mineral water. After a 7-day wash-out period, each subject underwent an oral load with mineral water alone under the same conditions. Urine specimens were collected before (for 120 min) and after each oral fluid load (for 180 min). Urinary flow was significantly increased after both grapefruit juice (46+/-26 vs 186+/-109 ml/h, p = 0.01) and mineral water (42+/-16 vs 230+/-72 ml/h, p=0.001) compared to baseline. Compared to mineral water, grapefruit juice significantly (p=0.021) increased urinary excretion of citrate (25.8+/-9.3 vs 18.7+/-6.2 mg/h), calcium (6.7+/-4.3 vs 3.3+/-2.3 mg/h, p=0.015) and magnesium (2.9+/-1.5 vs 1.0+/-0.7 mg/h, p=0.003). Citrus fruit juices could represent a natural alternative to potassium citrate in the management of nephrolithiasis, because they could be better tolerated and cost-effective than pharmacological calcium treatment. However, in order to obtain a beneficial effect in the prevention of calcium renal stones a reduced sugar content is desirable to avoid the increase of urinary calcium due to the effect of sugar supplementation.