Adenosine may be an important metabolic regulator of coronary blood flow during active hyperemia in the newborn. In this study, the adenosine uptake blocker dipyridamole (DPY) and receptor antagonist theophylline (THEO) were used to assess the role of adenosine in the reactive hyperemic response of the neonatal heart. Eighteen anesthetized, open-chest lambs were instrumented with aortic and coronary sinus catheters as well as an extracorporeal shunt to the circumflex coronary artery incorporating a 2.0-mm electromagnetic flow transducer. Ten-second occlusions of the circumflex coronary artery catheter were performed, and the resulting reactive hyperemia was used to determine peak hyperemic blood flow (PHF), duration of hyperemia, and the blood flow repayment. These values were determined prior to treatment and 30 min following administration of a saline vehicle, DPY (0.2 mg/kg) or THEO (5 mg/kg). DPY resulted in increases in PHF from 220 +/- 12 to 247 +/- 14 ml/min/100 g heart tissue (P less than 0.05), durations of hyperemia from 29 +/- 2 to 38 +/- 2 sec (P less than 0.01), and blood flow repayments from 65 +/- 2 to 102 +/- 4 ml/100 g (P less than 0.001). THEO resulted in decreases in PHF from 224 +/- 15 to 198 +/- 12 ml/min/100 g (P less than 0.05), durations of hyperemia from 28 +/- 2 to 22 +/- 2 sec (P less than 0.05), and blood flow repayments from 64 +/- 2 to 46 +/- 2 ml/100 g (P less than 0.01). The data indicate that DPY enhances reactive hyperemia while antagonism of adenosine with THEO attenuates it. These results suggest that adenosine plays a role in mediating reactive hyperemia in the newborn heart.