Cercarial toxin, a protein purified from Leiurus quinquestriatus venom and toxic to Schistosoma mansoni cercariae, was examined for its effects on frog twitch muscle fibres. In concentrations of 3.4-12 microM the toxin, after a delay of several minutes, produced a slowly developing depolarization of the resting membrane and high frequency miniature endplate potentials associated with spontaneous firing of muscle fibre action potentials and twitching. The action potential duration increased from about 3 to more than 100 msec. In advanced stages of poisoning the amplitude of action potentials decreased while oscillations on the plateau level occurred. Short electrical pulses were followed by repetitive firing of prolonged action potentials, while long stimuli elicited long-lasting action potentials with oscillations on the plateau level. Addition of d-tubocurarine blocked spontaneous sub- and suprathreshold activity. Increasing the Ca concentration of the medium markedly shortened the action potentials and stopped repetitive firing. It is concluded that cercarial toxin interferes with the ionic permeabilities of frog twitch fibres in a way similar to that reported for crude venom or one of its highly toxic fractions in frog nerve.