Dissolution of calcium oxalate urinary calculi was studied in vitro. Rate constants were calculated by measuring the concentration of calcium in solution during dissolution. Various irrigating agents, including ethylenediaminetetraacetic acid (EDTA) and other calcium-chelating substances, were tested at different concentrations and pH values. EDTA was the most effective agent in dissolving calcium oxalate calculi. When EDTA was used, the rate of dissolution depended on both concentration and pH. At a pH of 7.5 or 10.0, the rate of dissolution increased progressively with the EDTA concentration. At each concentration tested, dissolution was faster at a pH of 10.0 than at a pH of 7.5. Calculated rate constants were extrapolated to determine whether in vivo irrigation with EDTA solutions is clinically practical. Even at an EDTA concentration of 0.03 M at a pH of 7.5, a two mm. calculus could be dissolved within 48 hr. Although dissolution of calcium oxalate calculi is not a practical first-line treatment, it might be a useful adjunct to percutaneous stone removal or extracorporeal shock wave lithotripsy.