The treadmill exercise test (TET) is evaluated by exercise-induced ST-segment depression (delta ST). However, the depression sometimes only appears during the post-exercise period. Depression appearing only during the post-exercise period may be as useful as depression during exercise to predict coronary artery disease, but little is known about factors that may affect ST depression after exercise. The clinical significance and mechanism of post-exercise ST depression were investigated in patients with coronary artery disease. Target heart rate- or symptom-limited TET was performed in 531 male patients with definitive effort angina pectoris or myocardial infarction using the Bruce protocol. Patients were divided into four groups according to delta ST during exercise and 1-2 min after exercise; 1) no TET or post-exercise delta ST (Nn, n = 192), 2) only post-exercise delta ST (Np, n = 36), 3) only TET delta ST (Pn, n = 112), 4) both TET and post-exercise delta ST (Pp, n = 66). Patient profiles, parameters during TET, echocardiographic and coronary angiographic findings and outcome during the year after TET were compared between the Nn and Np or Pn and Pp groups. The percentage of patients treated with beta-blocker was higher in the Np than that in the Nn group (Nn: 45%, Np: 64%, p < 0.05) and systolic blood pressure declined at 1 min after exercise from peak exercise in the Nn, but not in the Np group (Nn: 175 --> 167 mmHg, p < 0.05; Np: 170 --> 170 mmHg, not significant). There was no difference in age, other parameters during TET, echocardiographic and coronary angiographic findings and outcome between the Nn and Np group. The incidence of right coronary artery stenosis and that of patients with multi-vessel disease were higher in the Pp than those in the Pn group (Pn: 41%, 58%, Pp: 65%, 73%, both p < 0.05). The occurrence of chest pain during exercise was higher in the Pp than the Pn group in spite of less delta ST at peak exercise. However, systolic blood pressure declined after exercise in the Pn group, but not in the Pp group (Pn: 164 --> 158 mmHg, p < 0.05; Pp: 166 --> 164 mmHg, not significant). These results confirmed that the clinical significance of post-exercise delta ST in patients without TET delta ST differs from that in patients with TET delta ST and suggests that post-exercise delta ST without delta ST during exercise may be associated with an abnormal response to imbalances in the cardiovascular sympathetic system in the post-exercise period rather than with myocardial ischemia.