The effect of diuretics on endolymphatic hydrops, which was produced by obliteration of the endolymphatic duct and sac in guinea pigs, was determined by statistical analysis of volumetric changes in the scala media. When acetazolamide was administered orally at 159 to 434 mg/kg per day for a period of 30 days, endolymphatic hydrops did not reach the extent of distension shown in animal ears without drug treatment. No difference was seen in animals with one month of drug treatment followed by three additional months without treatment. This result suggests that acetazolamide has the effect of reducing endolymphatic hydrops only during the period of drug administration. On the other hand, there appeared to be no effect, statistically, on hydrops in animals which were treated with chlorthalidone 72 to 182 mg/kg every other day for one month with survival times varying from one to four months. The effect of this drug favorably reported for the treatment of Meniere's disease symptoms is not demonstrated on endolymphatic hydrops, but rather is likely to involve other mechanisms. There was no essential difference in the extent of cochlear sensory and neural atrophy in the inner ears of animals with or without these drug treatments.