The venom of Micrurus spixii, a coral snake dispersed throughout the Amazon Valley induces neuromuscular blockade in the rat phrenic nerve-diaphragm preparation and in the chick biventer cervicis nerve-muscle preparation. In both tissues, the venom does not depress the twitch response elicited by direct muscle stimulation. The depolarization produced by carbachol in the rat diaphragm and the contractures induced by acetylcholine (ACh) in the denervated rat hemidiaphragm and in the chick biventer cervicis muscle are inhibited by low venom concentrations. The frequency and, in several experiments, the amplitude of the miniature end-plate potentials (m.e.p.p.s) are increased by the venom. The m.e.p.p. amplitude always decreases before their disappearance. 3,4-Diaminopyridine (3,4-DAP) antagonizes the effect of the venom on neuromuscular transmission in the rat phrenic nerve-diaphragm and on the depolarization produced by carbachol in this preparation. It also antagonizes the venom-induced blockade of the m.e.p.p.s and increases the end-plate potential (e.p.p.) after the blockade produced by the venom in the rat phrenic nerve-diaphragm. The 3,4-DAP antagonistic effect on the postsynaptic action of the venom suggests that desensitization of the end-plate receptors is induced by the venom and is the main cause of the neuromuscular blockade that it produces.411933