It has been suggested that the myocardium is able to recruit endogenous protective mechanisms in response to repeated ischemia and reperfusion. We set out to study whether this is manifested in patients with coronary artery disease in the form of fewer signs of myocardial ischemia during the second of two successive exercise tests and whether any relations exist between ischemia adaptation and findings at cardiac catheterization. Twenty-one patients with typical angina pectoris symptoms underwent two repeated bicycle exercise tests with identical protocols, followed by cardiac catheterization and coronary angiography the next day. The first exercise test was discontinued whenever a 2 mm ST depression in the electrocardiogram (ECG) was achieved or further exercise was limited by symptoms. The second exercise test was performed after disappearance of the symptoms or ST depression or both. Kaplan-Meier survival analysis for the appearance of a 1 mm ST depression demonstrated improved ischemia tolerance during the second test, when the required time for its appearance was significantly longer (6.5 +/- 0.8 min vs 4.5 +/- 0.5 min; p = 0.005). The maximal intensity of anginal pain was lower during the second exercise (2.2 +/- 1.0 min vs 0.7 +/- 0.3 min in Borg's scale; p