The diagnosis of ischemic heart disease by radionuclide ventriculography (RNV) is performed on the basis of an abnormal response of the left ventricular ejection fraction and the occurrence, or aggravation, of regional wall motion abnormality during exercise. However, the abnormal wall motion observed by RNV at rest is improved in some patients with coronary artery disease during exercise. We examined the clinical features of such patients who showed a paradoxical response of regional wall motion. The left ventricle was divided into 4 segments: anteroseptal, apical, inferior and posterolateral. The degree of wall motion of each segment was classified into 5 grades and scored according to a 5 point system: 4 = normokinesis, 3 = hypokinesis, 2 = severe hypokinesis, 1 = akinesis and 0 = dyskinesis. The wall motion score (WMS) was calculated as the sum of each segment score. If the WMS increased by 2 points or more during exercise, the case was defined as having shown significant improvement of wall motion. Improvement in WMS was found in 26 (12%) of 209 serial patients who underwent exercise RNV, exercise thallium myocardial scintigraphy and coronary angiography. Clinically, half of these patients had a variant form of angina pectoris. With respect to coronary lesions in the segments with reversible asynergy, 12 patients had 0 vessel disease, 8 had lesions with stenosis of less than 75% and 3 showed an adequate collateral circulation. Redistribution found on the exercise thallium myocardial scintigram at the same sites of improved wall motion was identified in only 1 patient. An analysis of patients with paradoxical improvement of wall motion during exercise suggests the involvement of coronary spasm, an improvement of coronary flow reserve, such as could be produced by regression or recanalization of the main lesions, or establishment of significant collateral circulation.