Arbutamine is a new catecholamine designed for use as a pharmacologic stress agent. This study compared the sensitivity of arbutamine with symptom-limited exercise to induce echocardiographic signs of ischemia. Arbutamine was administered by a computerized closed-loop delivery system that controls the infusion rate of arbutamine toward a predefined rate of heart rate increase and maximum heart rate limit. Beta blockers were stopped > or = 48 hours before both tests. Stress was stopped for intolerable symptoms, or clinical, electrocardiographic or echocardiographic signs of ischemia (new or worsening wall motion abnormality), target heart rate (> or = 85% age predicted maximum heart rate), or plateau of heart rate response. Thirty-seven patients were entered into the study (35 arbutamine and exercise, 1 arbutamine only, 1 exercise only), of which 30 had angiographic evidence of coronary artery disease (> or = 50% lumen diameter narrowing). Rate-pressure product increased significantly in response to both stress modalities (p < 0.001) and was significantly greater with exercise (11,308 +/- 2,443) than with arbutamine (9,486 +/- 2,479, p < 0.001). The time to maximum heart rate was longer during arbutamine stress echocardiography than during exercise testing (17.3 +/- 9.4 versus 9.3 +/- 4.2 minutes, respectively, p < 0.001). There were more patients with interpretable echo data for arbutamine (82%) than for exercise (67%). Sensitivity for recognition of myocardial ischemia was 94% (95% confidence interval 70% to 100%) and 88% (95% confidence interval 62% to 98%), respectively. The most frequent adverse events during arbutamine (n = 36) were dyspnea (5.6%) and tremor (5.6%). Two arbutamine stress tests were discontinued due to arrhythmias: 1 patient had premature atrial and ventricular beats, and the other had premature atrial contractions and atrial fibrillation. Arrhythmias were well tolerated and resolved without sequelae. In conclusion, the sensitivity of arbutamine to induce echocardiographic signs of ischemia was similar to that of exercise despite a lower rate-pressure product. Arbutamine was well tolerated and provides a reliable alternative to exercise echocardiography.