Although solutions containing disodium ethylenediaminetetraacetic acid (EDTA) will dissolve calcium oxalate stones in vitro, the safety of such solutions as urinary tract irrigants is questionable. These studies were designed to assess the degree of urothelial damage produced by the mildest EDTA formulation which has been reported to be effective. Rabbit bladders were irrigated antegrade via a ureterotomy for 20 hours and then removed for histological examination. A 0.03 M solution of disodium EDTA at pH 7.5 produced considerably more urothelial injury than did an otherwise identical solution of calcium EDTA (p = 0.006). The bladders from the latter group were undistinguishable from those irrigated with saline. As prior saturation of EDTA with calcium completely eliminated the tissue injury, these studies indicate that the same calcium chelating property which makes this chemical effective also makes it toxic. There was enough tissue damage from the relatively mild formulation used to suggest no EDTA solution yet formulated is safe for clinical use.