Potent cardioinhibitory vagal reflex resulting in bradycardia and hypotension has been observed under particular conditions of transmural inferior ischemia and its reperfusion - such as that observed with acute infarction. However, whether exercise-induced ischemia with ST depressions, that is subendocardial and that might be recurrently experienced in daily activities, can evoke this reflex remains unknown. In patients with exercise-induced ST depressions due to either inferior (right coronary artery stenosis, RCA, n=52) or anterior ischemia (left anterior descending artery stenosis, LAD, n=51), we evaluated post-exercise vagal activity (0 to 6 min) by the time constant of heart rate (HR) decay and HR variability by 30-sec averages of the absolute values of successive RR interval differences (RR). Exercise parameters were similar between the groups. Time constant was slightly but significantly shorter in RCA than in LAD patients (79 ± 24 vs. 93 ± 29 sec, p < 0.01). More significantly, &#8710;RR early after exercise (0.5 - 2.5 min) was approximately twofold greater in RCA than in LAD patients (+76 to +118%, p < 0.001), indicating pronounced vagal activity stimulated by inferior ischemia. Revascularization prolonged time constant (p < 0.05) and attenuated recovery RR in RCA patients (p < 0.05, n=10), but did not change both parameters in LAD patients (n=12). As well as acute inferior infarction, exercise-induced inferior subendocardial ischemia, that might recurrently occur in daily activities, activates the cardioinhibitory reflex. These new findings must be taken into account in interpreting vagal activity in patients with coronary artery disease.