Coronary thrombolysis in patients frequently unmasks high grade residual stenosis. To determine whether beneficial effects of reperfusion are compromised by critical residual coronary stenosis, 14 dogs were instrumented with an external left anterior descending coronary artery balloon occluder, Doppler flow probe and adjustable screw clamp. In eight of the dogs, critical stenosis (abolition of reactive hyperemia after a 20 s occlusion; 95.7 ± 1.0% cross-sectional area reduction) was induced before occlusion and maintained. In the control group (n = 6), no stenosis was induced Each dog was subjected to 2 h of myocardial ischemia followed by balloon deflation and 24 h of reperfusion. Myocardial blood flow assessed with microspheres was similar during balloon inflation in both groups and indicative of profound ischemia. Transmural blood flow to the reperfused zone assessed 1 min after balloon deflation was significantly greater in control dogs without residual stenosis (383% of normal compared with 120% of normal in dogs with stenosis) (p < 0.01). Compromise of transmural flow persisted in dogs with stenosis (85% compared with 121% of normal in control dogs after 1 h, p < 0.05; and 49% compared with 68% after 24 h of reperfusion, p < 0.05). Diminution of subendocardial blood Row after reperfusion was particularly marked. The extent of infarction was greater in the heart of dogs with residual stenosis. Thus, residual critical coronary stenosis compromises nutritional perfusion and salvage of reperfused myocardium after recanallzation. These observations underscore the need for prompt identification of patients with high grade residual stenosis early after coronary thrombolysis and the potential value of angioplasty or coronary surgery in selected patients soon after initial recanalization.