The mechanism of cholinolytic action of dipyroxime--reactivator of the phosphorylated acetylcholinesterase were investigated in the rat diaphragm muscle by voltage-clamp technique. Dipyroxime reduced the amplitude and prolonged the decay of the miniature end-plate currents (MEPC) without affecting its exponential nature. Current-voltage relationship exhibited negative conduction in the hyperpolarized region. Dipyroxime increased the voltage dependence of the time constant of MEPC decay (the membrane potential alteration necessary for e-fold change of the decay time constant reduced from 80 to 35 mV). It was concluded that dipyroxime is a very fast blocker of the open end-plate channels.