Adenosine is a metabolic vasodilator of the coronary vessels in the adult. Whether it plays a similar role in the regulation of coronary blood flow (CBF) in the newborn is not known. We evaluated changes in adenosine release during periods of decreased oxygen supply (hypoxia) and increased oxygen demand (dobutamine infusions). In anesthetized open-chest lambs (age 1 to 8 days), aortic and coronary sinus adenosine concentrations, circumflex CBF, and myocardial oxygen consumption (MVO2) were measured. Adenosine was assayed by high-performance liquid chromatography, and the release of adenosine was calculated as the product of the aortic-coronary sinus plasma level difference and CBF in milliliters per minute per 100 gm myocardial tissue. Control values were obtained when the lambs were ventilated with 60% oxygen. In the first series of experiments, hypoxemia resulted in an increase in CBF from 120 +/- 5 to 171 +/- 8 ml/min/100 gm (p less than 0.01). This was associated with sixfold increase in adenosine release. In a second set of experiments the intravenous infusion of dobutamine resulted in parallel increases in MVO2 and CBF. Concomitantly, adenosine release increased by fivefold. There were significant linear relationships between MVO2 and CBF (r = 0.96; p less than 0.01), MVO2 and adenosine release (r = 0.69; p less than 0.002), and adenosine release and CBF (r = 0.71; p less than 0.002). These data support the hypothesis that adenosine may play an important role in the regulation of CBF in the newborn lamb.