Neuromuscular transmission in the Chinese cobra Naja naja atra was not affected by its own toxin (cobrotoxin) at a concentration of as high as 100 microM, while in the frog a concentration of less than 0.1 microM cobrotoxin depressed the amplitude of the end-plate potential to less than 10% of its original value within 30 min or directly blocked the nerve-evoked muscle action potential. The lack of effect of cobrotoxin was also observed in the nerve-muscle preparations from a pit viper (Agkistrodon blomhoffii brevicaudus) and three species of non-poisonous snakes (Elaphe dione, Elaphe bimaculata and Elaphe rufodorsata). On the other hand, the snake preparations were sensitive to the blocking effect of D-tubocurarine and less sensitive to that of atropine, indicating that the nicotinic acetylcholine receptor is responsible for transmission between the nerve and the skeletal muscle of the snake. We suggest that the snake nicotinic cholinergic receptor lacks the cobrotoxin binding-site.