The purpose of these studies is to investigate specific metabolic and neurogenic factors and their interaction in the regulation of cerebral blood flow of the fetus and the newborn during normoxic and hypoxic states of tissue oxygenation. Physiological evidence suggests that accumulation of adenosine in extracellular and perivascular spaces plays a major role in the regulation of vascular resistance during conditions of inadequate oxygen supply. The importance of adenosine to cerebral blood flow in the developing animal has not been established. The present study will attempt to evaluate the role of adenosine in the regulation of cerebral blood flow in the fetal and newborn lamb under conditions of normoxic and hypoxic states. Cerebral vessels receive rich supply of sympathetic nerves from the superior cervical ganglion. The importance of these nerves in regulating cerebral blood flow in adults is unclear. Physiological evidence suggests that these nerves are present at birth and may influence flow more profoundly in newborns than adults. Studies are proposed to determine the efficacy of sympathetic nerve stimulation and physiological significance on cerebral blood flow. Present pharmacological and physiological evidence has demonstrated that adenosine inhibits sympathetic effects by inhibiting neurotransmission. This study will also attempt to evaluate the possibility that adenosine modulates the efficacy of sympathetic stimulation in the newborn lamb. Using the specific response of mitochondrial respiratory activity of tissues as an indicator, these studies will possibly also define limits of tissue oxygenation. The results of this research will add to the understanding of the regulation of cerebral circulation and tissue oxygenation in the fetus and newborn and further elucidate maturational aspects of sympathetic control.