This study was designed to test the hypothesis that A2 adenosine receptors mediate the vascular responses to intravenous infusions of dipyridamole. We tested this hypothesis using theophylline which has been reported to block A2 adenosine receptors and thereby attenuate the vasodilation caused by adenosine. We used twenty four anesthetized lambs that were between 7 and 17 days of age. Basal systemic and pulmonary vascular resistances of each animal were increased with the thromboxanemimietic U46619. A theophylline dose commonly used in humans (5.0 mg/kg infused over 30 min followed by 1.0 mg/kg/h) resulted in negligible changes in the vasodilation caused by either dipyridamole or adenosine. However, a tenfold greater theophylline dose significantly attenuated the vasodilation caused by adenosine, yet the attenuation in vasodilation caused by dipyridamole remained negligible. In addition, dipyridamole caused a weakly preferentialpulmonary vasodilation (p=0.05) whereas adenosine caused a strongly preferential systemic vasodilation (p<0.01). We also found that the responses to infusion rates of adenosine greater than 0.3 mg/kg/min caused atrioventricular dissociation and profound slowing of ventricular contraction rates- effects that were blocked by theophylline (p<0.05) and potentiated by dipyridamole (p<0.05). All of these findings are consistent with previous reports of dipyridamole's cardiovascular effects and they suggest that dipyridamole causes systemic and pulmonary vasodilation via predominantly A2 adenosine receptor independent mechanisms.