The present study was undertaken to determine whether adenosine attenuates cochlear dysfunction induced by transient ischemia. Adenosine or erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, was administered by perilymphatic perfusion to albino guinea pigs that were subjected to cochlear ischemic episodes of 30-minute duration. The threshold shift of the compound action potential (CAP) from the preischemic value was significantly reduced in the animals perfused with EHNA 1 hour after the onset of reperfusion. However, perfusion of adenosine at concentrations of 100 micromol/L to 10 mmol/L did not reduce the postischemic CAP threshold shift by either 1 hour or 4 hours after the onset of reperfusion. These results suggest that the elevation of the adenosine concentration did not exert a protective effect on the cochlear ischemia-reperfusion injury, and that the protective action of EHNA is unrelated to elevating the adenosine concentration.