This study tested the hypothesis that in the chronically hypertrophied left ventricle pacing stress may cause abnormalities of perfusion that result in myocardial ischemia. Left ventricular hypertrophy (LVH) was produced by banding the ascending aorta of 10 dogs at 6 weeks of age, and studies were carried out after the animals had reached adulthood and when mean left ventricular/body weight ratio was 74% greater than in 8 control dogs. Myocardial blood flow was measured with microspheres during pacing at 100, 200, and 250 beats/min, while aortic and coronary sinus blood samples were obtained for determination of concentrations of lactate and the adenosine metabolites inosine and hypoxanthine. In the control dogs, increasing heart rates were associated with an increase in mean myocardial blood flow while subendocardial flow was maintained at a level equal to or greater than subepicardial flow. Myocardial lactate uptake ranged from +60% to -5%, and adenosine metabolites were not detected in coronary sinus blood (<0.5 μM/l). In 4 dogs that underwent aortic banding no production of lactate or adenosine metabolites was observed at any heart rate; in these animals subendocardial flow was maintained at a level equal to or greater than subepicardial flow at all pacing rates. The remaining 6 dogs with LVH demonstrated net lactate production significantly greater than control during pacing at 250 beats/min; 5 of these 6 animals also produced adenosine metabolites. In these 6 animals mean myocardial blood flow failed to increase as the pacing rate was increased from 200 to 250 beats/min, and pacing at 250 beats/min was associated with a transmural redistribution of perfusion away from the subendocardium (subendocardial/subepicardial blood flow ratio = 0.50 ± 0.05). These findings demonstrate that perfusion abnormalities may occur in the chronically hypertrophied heart during rapid cardiac pacing and that these result in myocardial ischemia.