The work which led up to the investigation described in this paper was concerned with the influence of adrenaline on the action of acetylcholine or on tissue functions normally elicited by acetylcholine. Previously experiments were carried out on animals with a normal circulation or on perfused organs, and any adrenaline effects observed were accompanied by vasoconstriction, so that it was conceivable that its action was due to vascular changes.The improvement in the transmission of impulses along the motor nerve (Bulbring and Burn, 1939) or the lowering of threshold to submaximal stimuli applied to the sciatic nerve (Bulbring and Whitteridge. 1941) by injecting adrenaline into the circulation might have been due to changes in the distribution of blood in the vascular bed of the nerve trunk leading to an alteration of electrical resistance. However, there was a discrepancy in time relations, lhe increased nervous excitability lagging behind and long outlasting the vascular effect of adrenaline.In fatigued skeletal muscle adrenaline-and other vasoconstrictor substances ----augment muscle contractions (Bulbring and Burn, 1940), but Maibach (1928) and Corkill and Tiegs (1933) obtained the same result on frog muscle suspended in a bath, showing thereby that the action of adrenaline on the fatigued nerve muscle preparation can be observed without its vascular action. Presumably, in fatigue, neuromuscular transmission gradually fails and is restored by adrenaline. When, for instance, Bulbring and Whitteridge (1941) recorded muscle tension and nerve action potentials, a striking absence of parallelism between the effect of adrenaline on muscle and nerve was observed. At a time when no effect of adrenaline on the nerve response to maximal shocks at 1 per sec. could be seen, 100 per cent increase was seen in the fatigued muscle.In non-fatigued skeletal muscle stimulated indirectly with maximal shocks, it was found that adrenaline augmented the effect of prostigmine. The results were taken to indicate that adrenaline facilitates neuromuscular transmission and increases the action of acetylcholine on the muscle (Bulbring and Burn, 1942). Though the dose of adrenaline used was always the same, producing a similar degree of vasoconstriction each time. its effect on the muscle was dependent not only on the presence of prostigmine and on the amount of prostigmine given, but 3