Exercise generally aggravates ischemic myocardial dysfunction, presumably by increasing tissue oxygen demand out of proportion to the increase in supply. Nevertheless, resting left ventricular (LV) wall motion abnormalities can improve dramatically after upright exercise. To investigate this "paradoxical" phenomenon, we performed upright bicycle exercise equilibrium radionuclide ventriculography in 93 patients with angiographic coronary artery disease. Immediately after exercise, LV end-diastolic volume was similar to the resting level (1 +/- 22% of rest value), but end-systolic volume (ESV) was significantly below (p less than 0.05) that at rest (-11 +/- 32%) and LV ejection fraction increased significantly compared with rest (0.57 +/- 0.16 vs 0.51 +/- 0.13, p less than 0.05). Improvement in resting myocardial asynergy was frequent (115 of 330 abnormal segments), and was observed more commonly in patients without pathologic Q waves and in segments manifesting mild rather than severe asynergy. In 60 additional patients with resting asynergy who were also studied after nitroglycerin (NTG), there was 89% concordance of wall motion response in asynergic segments after exercise and NTG: 71 of 85 segments manifesting improvement with NTG also improved after exercise, and 157 of 172 segments without improvement with NTG also failed to improve after exercise. Despite the similar wall motion response, the mechanism of improvement is probably different from that produced by NTG. With NTG, preload (end-diastolic volume) and afterload (systolic blood pressure) were significantly lower than their resting control levels (p less than 0.05). These changes did not occur after exercise. Instead, an isolated, significant reduction in ESV was noted. These data support the hypothesis that catecholamine stimulation is responsible for paradoxical wall motion improvement after upright exercise.