A study of the effect of ethacrynic acid on guinea-pig blood, cerebrospinal fluid and perilymph Na and K is reported. After exposure to 50 mg/kg of ethacrynic acid administered over 48 h, the perilymph K, 1.6 h following the last injection, was found to be markedly elevated above control values (0.01 > P > 0.001). This change in K may result from ethacrynic acid inhibition of a membrane ATPase system. One speculation is that elhacrynic acid ototoxicity results from the inhibition of cochlear-duct membrane ATPase.