The action of uridine-5'-diphosphoglucose (UDPG) on the contractile response of the phrenic diaphragm preparation from guinea pig was investigated. UDPG activity was assayed on the preparation at rest or during the exercise; in this case indirect electrical stimulation of phrenic diaphragm preparation or direct stimulation of denervated or curarized muscle were employed. Krebs' solutions adequately modified with regard to glucose concentration were used. The effect of UDPG on the neuromuscular junction was also investigated by recording miniature end plate potentials. An effect of the drug on neuromuscular transmission and on glucose metabolism could be demonstrated.