The regulation of K+ and Na+ in the inner ear fluid of the guinea pig was studied after the application of saturated NaCl solution to the round window membrane. K+ and Na+ activities in the scala tympani increased rapidly and then decreased. K+ activity in the scala media increased immediately, but Na+ activity continued to increase during the period of observation. K+ activity in the scala vestibuli continued to increase in the observation period. Na+ activity in the scala vestibuli increased and then decreased. The endocochlear potential decreased immediately to approximately 20% of its initial level. Total activities of K+ and Na+ increased immediately and then decreased in both the scala tympani and scala media. The total activity of K+ and Na+ increased slowly and showed no regulatory decrease in the scala vestibuli. Thus, changing patterns in the total activity of K+ and Na+ were similar for the scala tympani and scala media, but not for the scala media and the scala vestibuli. Different patterns of K+ and Na+ activities among the three scalae indicate that their mechanisms for regulating inner ear fluid differ.