AbstractSingle muscle fibers from a typical case of hypokalemic periodic paralysis (HOPP) have been found to be depolarized in all test media and to be cathodally blocked after exposure to insulin. The diseased fibers also bind more insulin and consume more oxygen than controls. The hypothesis proposed is that increased amount or affinity of insulin binding on the HOPP muscles causes continual depolarization in the presence of normally subthreshold concentrations of circulating insulin. This is because of steady effects of the hormone on passive K+and Na+fluxes. Additional insulin causes rapid further depolarization with paralysis. Hypokalemia follows if the insulin increment is enough to stimulate active K+and Na+transport.