The association of the autonomic nervous system with coronary vasospasm has been controversial. The aim of the present study was to examine the involvement of the autonomic nervous system in coronary vasospasm by applying the head-up tilt (HUT) test to patients with coronary vasospastic angina. Fifteen consecutive patients with coronary vasospastic angina and without significant organic coronary stenoses underwent the HUT test. Prior to the test, coronary spasm was documented angiographically by using an intracoronary injection of acetylcholine or ergonovine. The HUT test was performed in the early morning and repeated in the afternoon if the test was positive in provoking angina pectoris and syncope or presyncope. If the test was negative, it was repeated under intravenous infusion of isoproterenol at a rate of 1-2 microg/min. The HUT test under isoproterenol infusion in the morning provoked vasospastic angina with syncope or presyncope in 9 of the 15 patients. In the test-positive group, heart rate was significantly reduced (104+/-17 beats/min to 84+/-25 beats/min, p<0.05), which preceded a reduction in systolic blood pressure (158+/-25 mmHg to 125+/-17 mmHg, p<0.001), angina attack and syncope. The HUT test without isoproterenol infusion in the morning and the HUT test in the afternoon with or without isoproterenol infusion failed to provoke angina. The heart rate reduction preceding reduced systemic blood pressure and anginal attack suggested that parasympathetic nerve excitation plays an important role in coronary vasospasm. The results also implied that the HUT test combined with isoproterenol infusion is useful for the provocation of coronary spasm.