Although liver is thought to be the major glucose-producing organ in vertebrates, it is not the major source responsible for the accumulation of glucose in frogs during burst activity. This is indicated by the absence of significant changes in liver glycogen levels during exercise, the inability of the maximal reported rate of hepatic glucose production in vitro to account for the increase in the glucose content of the frog, and from the observation that hepatectomized and normal frogs accumulate similar amounts of glucose in their muscles and body during exercise. We conclude that most glucose that accumulates in the body during exercise originates in muscle because two-thirds of body glucose is found in muscle and because the intracellular levels of muscle glucose rise well above plasma levels. The glucose that accumulates outside muscle is also likely to originate in muscle. The most likely metabolic source of the glucose produced by muscle is the glycogen hydrolyzed by amylo-1,6-glucosidase.