Adenosine and verapamil have successfully been used in the treatment of clinical no-reflow after direct angioplasty for acute myocardial infarction. However, their effects on anatomic perfusion defects in experimental myocardial ischemia/reperfusion are unknown. Thus the area of no-reflow (ANR), visualized after in-vivo staining of perfused tissue by thioflavin S (% of the risk area, RA, blue dye), and regional myocardial blood flow (radioactive microspheres) were determined in anesthetized open-chest rabbits after 30 minutes of occlusion and 120 minutes of reperfusion. Adenosine, administered intravenously during the entire reperfusion period, reduced vascular resistance in the RA at 120 minutes of reperfusion by 39% compared with controls (P < 0.053). However, in every animal, sizable perfusion defects developed and the ANR with adenosine treatment (29 +/- 3%) was not significantly different from saline controls (35 +/- 6%). Intravenous verapamil, given during the entire reperfusion period, reduced vascular resistance in the RA by 54% at 120 minutes of reperfusion (P < 0.03). But perfusion defects, visible in every animal, were similar in size between verapamil (38 +/- 5%) and saline (35 +/- 6%) groups. Therefore, neither treatment prevented or attenuated perfusion defects after ischemia/reperfusion despite reducing vascular resistance in the RA; hence vasospasm is not a major contributor to microvascular perfusion defects in this model.