Increased sympathetic drive has been suggested to play a role in the pathogenesis of syndrome X (angina pectoris, positive exercise testing, and angiographically normal coronary arteries). Heart rate variability (HRV) studies have shown that patients with syndrome X have an imbalance in autonomic nervous system activity (sympathetic predominance). However, it is not known if transient ST-segment depression which occurs in syndrome X during daily activities is related to this autonomic nervous system dysfunction. This study investigates the relation between the response of the autonomic nervous system, as assessed by HRV analysis, and the occurrence of transient ST-segment depression during 24-hour ambulatory electrocardiographic monitoring in 23 patients (4 men and 19 women, mean age 55 +/- 6 years) with syndrome X. The frequency-domain variables of HRV low-frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.40 Hz) power were measured at 6-minute intervals during the 30 minutes preceding the onset of transient ST-segment depression. Fourteen patients (61%) had > or = 1 episode of ST-segment depression in the 24 hours, whereas the remaining 9 patients (39%) had no significant ST-segment change. HRV measures differed according to whether or not ST-segment depression was associated with increased heart rate. Episodes of ST-segment depression associated with increased heart rate were preceded by a reduction of high-frequency power and an increase in the low-frequency--high-frequency ratio, whereas episodes of ST-segment depression not associated with increased heart rate showed no significant HRV changes. Low-frequency power remained unchanged irrespective of heart rate. Thus, in patients with syndrome X, a sympathovagal imbalance (sympathetic predominance due to vagal tone withdrawal) precedes episodes of ST-segment depression that are associated with an increased heart rate.