We examined the effects of anoxia and ethacrynic acid on the endolymphatic potential and cation activity in the superior ampulla of the guinea pig, using double-barrelled ion-exchanger microelectrodes. In normal guinea pigs the ampullar endolymphatic potential was +3.9±1.2 mV (n=32), the Cl− activity 130±4.6 mM (n=9), and the Na+ activity 18.4±4.4 mM (n=20). After anoxia, the ampullar DC potential decreased rapidly and reversed its polarity within 5 min. It then decreased gradually for 60 min and increased afterwards to approximately zero. K+ activity decreased gradually after a latency of 10 min, whereas Na+ activity increased. During the gradual decrease of a negative ampullar endolymphatic potential, an increase in Na+ activity was observed. Thirty minutes after the intravenous injection of ethacrynic acid (100 mg/kg), the potential began to decrease, changed to a negative polarity, and approached a maximum negative level 100 min after the injection. The decrease in K+ activity corresponded to the reduction of potential whereas Na+ activity remained unchanged. The DC potential of the endolymphatic sac in normal guinea pigs was + 14.7±5.1 mV (n=17). The Na+ concentration was 103.3±14.7 mM (n=14) and the K+ concentration was 11.6 ±0.8 mM (n=4). After anoxia, the DC potential decreased rapidly and approached 0 mV within 8 min. No negative potential could be observed. The Na+ concentration began to increase 2 min after anoxia and reached the extracellular Na+ concentration about 30 min later. No significant effect of intravenous administration of ethacrynic acid (100 mg/kg) on DC potential and Na + concentration could be observed. The results suggest the presence of a different ion transport system in the endolymphatic sac from that of the cochlea and the ampullae of the semicircular canals.