Twelve adults receiving halothane-nitrous oxide anaesthesia for elective surgery were investigated during suxamethonium-induced neuromuscular block, using the train-of-four twitch for measurement of both the degree of block and the magnitude of fade (decrease in fourth-to-first ratio). The residual neuromuscular block resulting from prolonged exposure to suxamethonium could be antagonized by bolus injections of suxamethonium itself, in doses which increased the block in Phase I. When self-antagonism was demonstrated, larger doses were necessary to increase the residual block, but only after overcoming the self-antagonizing effect. A biphasic response, first antagonizing then increasing the block, was observed following injection of a single bolus of suxamethonium. The self-antagonizing effect was more obvious in the fourth twitch of the train-of-four, resulting in a marked decrease in train-fo-four fade (increase in train-of-four ratio). It was concluded that self-anatagonism may be an important cause of tachyphylaxis in suxamethonium-induced neuromuscular block in man.