The clinical use of oral Fe chelators for the treatment of Fe-storage disease in birds requires evaluation. In this study, the efficacy of the Fe chelator deferiprone in reducing hepatic Fe stores, its effects on hematologic, biochemical, and plasma Fe parameters, and its potential toxicity during a 30-day treatment period were investigated in a controlled setting using two model species, the white leghorn chicken (Gallus gallus f. domestica) and the domestic pigeon (Columba livia). A second phase of the study investigated deferiprone-related Fe elimination in the excreta. Deferiprone, administered orally at a dosage of 50 mg/kg twice daily to birds that had been experimentally Fe loaded, significantly reduced hepatic Fe concentrations compared with levels in Fe-loaded and non–Fe-loaded controls. There were no significant alterations in routine clinical hematologic or biochemical parameters, although decreased transferrin saturation was noted in both species. Side effects associated with deferiprone administration were decreased weight gain and significant decreases in plasma Zn concentrations. No mortalities occurred in the pigeons, but there were three deaths in the deferiprone-treated group of Fe-loaded chickens, most likely associated with acute reduction of Fe required for normal enzymatic processes. Histologic changes associated with deferiprone treatment were not noted. Deferiprone caused a dose-dependent increase of Fe in the excreta at oral dosages of 50 and 75 mg/kg once daily in both species. Deferiprone is a promising, orally active Fe chelator for the treatment of Fe overload in birds, although its potential side effects need to be considered.