Since the usefulness of high-dose cyclophosphamide is often limited by hemorrhagic cystitis, and the use of sulfhydryl-containing compounds prevents this side effect, this study was carried out to compare the uroprotective efficacy of 2-mercaptoethane sulfonate (MESNA) with that of reduced glutathione. In experimentally cyclophosphamide-induced urotoxicity in mice, the protective efficacy and potency of these thiols were similar, since both agents afforded complete protection in the same dose range. This finding suggests that these compounds are suitable sources of urinary thiols. Although the rationale for the clinical use of these protectors is similar, glutathione may have therapeutic advantages over MESNA because of a wider margin of safety and multiple protective actions displayed by the tripeptide thiol.