The effect of ethacrynic acid (EA) at different blood O(2) saturations on cochlear potentials of guinea pigs was investigated. All 18 young healthy guinea pigs received 50 mg/kg/h of EA intravenously and were divided into three groups: first group, normal (90.00+/-6.30-86.17+/-4.83 mm Hg); second group, lower Po(2) (78.00+/-4.74-70.00+/-4.42 mm Hg); and third group, high Po(2) (174.40+/-13.41-179.00+/-26.15 mm Hg). The partial pressure of oxygen (Po(2)), the partial pressure of carbon dioxide (Pco(2)), and the pH of the blood were measured before EA administration and at the end of the experiment (3 h later) by drawing blood samples from the contralateral carotid artery. Cochlear potentials-endocochlear potential (EP), cochlear microphonics (CM), and action potentials (AP)-were recorded by standard methods from the first turn of the cochlea. Experimental data seem to indicate that elevation of the Po(2) to 174-179 mm Hg during relatively high doses of EA treatment prevents the declines in cochlear potentials which were observed in the first and second groups (normal and lower Po(2)), and preserves active ion transport which is responsible for the generation of cochlear potentials. These data suggest a means by which to reduce the ototoxic effect of EA and possibly indicates a method of treatment for hearing loss which developed after the administration of EA.