In patients unable to perform a maximal exercise test, dipyridamole single-photon emission tomography (SPET) has a higher capacity than exercise SPET to detect coronary artery disease (CAD). However, in patients with myocardial ischaemia who are able to perform a maximal exercise test, it is not known whether these two tests may be equally used to assess the areas of myocardial ischaemia. This study was aimed at comparing the results provided by dipyridamole and exercise SPET in CAD patients with documented exercise myocardial ischaemia. Forty CAD patients who had undergone exercise thallium-201 SPET and who had myocardial ischaemia documented by an unequivocally positive exercise test underwent an additional 201Tl SPET study after dipyridamole infusion and low-level (40 W) exercise. The extent of defects was compared between the two tests and predictors of discrepant results were sought among data from exercise testing and coronary angiography. The extent of SPET defects was equivalent between the two tests in only 11 patients (28%), larger defects being observed with exercise in 18 [average difference: 12%+/-5% of left ventricle (LV)] and with dipyridamole in 11 (average difference: 15%+/-11% of LV). The best independent predictors of discrepancies between the two tests were: (1) increase in heart rate at exercise SPET, with defects being smaller at exercise than after dipyridamole in none of the patients with an increase >60 bpm (0/14), but in 42% of the others (11/26; P=0.004); and (2) an ischaemic territory related to a <70% coronary stenosis, for which SPET defects were always induced at exercise (10/10) but in only 30% (3/10) with dipyridamole (P=0.0004). Exercise and dipyridamole SPET provide different estimates of myocardial ischaemic areas. Dipyridamole allows the unmasking of perfusion abnormalities in patients who have low increases in heart rate at exercise SPET. However, dipyridamole is also much less efficient at inducing perfusion abnormalities in the ischaemic areas supplied by coronary stenoses of intermediate severity at rest angiography.