In addition to therapy with anticholinesterases, ephedrine is sometimes used to improve muscle strength in myasthenia gravis, with variable results. The efficacy of ephedrine was tested in rats with a alpha-bungarotoxin-induced model of myasthenia gravis. The rats showed a drooping lower lip and impaired capability of drinking. Injections of neostigmine caused an improvement of the position of the lip. Ephedrine caused some improvement. However, ephedrine had no effect, either on the lower lip or on water consumption, when the sleep-wake cycle was reversed and the rats had their active period during day time. It was concluded that the effect of ephedrine was unspecific and probably due to arousal from drowsiness. The results suggest, therefore, that the variability of the effect of ephedrine in myasthenic patients is unrelated to neuromuscular transmission per se but rather due to a difference in susceptibility to arousal.