The influence of hormones upon the peripheral nervous system has been demonstrated mainly in isolated systems. These studies correlate muscle action potential (AP), amplitude, and contraction height with variations in ACTH levels in situ in the rat. The sciatic nerve was stimulated without being cut (5/sec; 0.1 msec duration; supermaximal strength). Gastrocnemius APs and contractions were then recorded for 30 min of stimulation and again after rest. Muscle temperature was also recorded. The effects of endogenous ACTH induced by cold stress (3°C for 4 h) and the administration of 10 mU ACTH were investigated in normal, adrenalectomized and hypophysectomized rats. The results indicate that increasing ACTH titers increase AP and contraction amplitude and diminish fatigue in all groups. Hypophysectomy, with a concomitant decrease in ACTH, has the opposite effect upon these parameters. Muscle temperature does not appear to be a causative factor. The possibility that ACTH may act directly on nerve or muscle membrane, or on the neuromuscular junction, is discussed.