Endocochlear potential (EP) and eighth nerve action potential (AP) were measured in chinchillas. We investigated the interaction of quinine with the loop diuretics furosemide and ethacrynic acid to determine whether the cochlear effects of these agents are attenuated by pretreatment with quinine. Animals were injected with either furosemide, 25 mg/kg intravenously (IV), or ethacrynic acid, 15 mg/kg IV. Control animals injected without pretreatment were found to have a large decrease in EP, with a decrease of compound action potentials (CAP) amplitude and an elevation of CAP threshold. Animals pretreated with quinine, 25 mg/kg, were found to have a significantly smaller reduction of EP and CAP amplitude following injection of either diuretic. No significant differences in urine volumes were noted between experimental and control groups. Quinine is known to cause nonspecific changes in the membranes of epithelial cells, which may cause alterations of the transport of organic anions by such tissues. Such an effect on epithelial cells in the cochlea may cause reduced uptake of loop diuretics in this organ, resulting in reduced toxicity.