Several known respiratory inhibitors were found to prevent cantharidin-induced acantholysis and also to block respiration in specimens of whole skin from the hairless mouse. The length of incubation required for the appearance of acantholysis was directly related to the rate of respiration, and inhibitors which produced only partial inhibition of respiration merely delayed the time of appearance of the lesion. No evidence could be obtained for a stage of the production of acantholysis in which respiration was not required. It was found that glycolysis can replace respiration in the acantholytic process. From this it was concluded that the acantholysis induced by cantharidin requires adenosine triphosphate.