The action of alpha-latrotoxin (alpha-LTx), the major toxic component from black widow spider venom, was studied on mammalian motor nerve endings and fibers. Electrophysiologic recordings of presynaptic and postsynaptic responses at early stages after the application of different doses of alpha-LTx showed massive transient increases in transmitter release and changes in the configuration of presynaptic currents. Later, a loss of invasion of terminals by nerve impulses occurred, whereas the impulse conduction in nerve fibers was unmodified. These results support the idea of a selective effect of alpha-LTx on presynaptic membrane excitability.