The effect of equinatoxin II on the excitability of nerve and muscle membrane was examined. Neuromuscular transmission was assessed indirectly by measurement of isometric muscle contractions. Membrane currents and potentials were measured by means of vaseline-gap voltage-clamp and current-clamp methods on single isolated skeletal muscle fibres. 10 nM equinatoxin II induces spontaneous twitches of skeletal muscle fibres provided that the neuromuscular junction remains intact. In curarized muscles and by use of higher final concentrations of equinatoxin II prolonged contractures were observed. This may be explained by a pore formation in the muscle membrane. An increase in the leakage conductance of skeletal muscle fibres supports this hypothesis.