The dissolutive effects of sodium fluoride on human calcium stone particles were investigated in an in vitro model. Stone particles composed of 65% calcium oxalate and 35% calcium phosphate dissolved in a dose-dependent fashion with NaF exposure. Stone particles exposed to 60 mM NaF had a 17% reduction in particle mass after 24 hours and a 62% reduction after 7 days in comparison with experimental controls bathed in physiologic normal saline. The systemic toxicity of the dose of oral fluoride necessary to achieve the optimal tested urinary concentrations would likely preclude oral administration, but NaF may have an adjunctive role in upper urinary tract irrigation for residual stone fragments after lithotripsy or in chronic low-dose oral administration for prophylaxis against recurrent calcium nephrolithiasis.