Anxiety disorders are associated with an increase in cardiovascular mortality. Studies using heart rate (HR) and QT interval variability measures suggest a decreased cardiac vagal function and a relatively increased sympathetic function in anxiety. This is important, as increased sympathovagal balance is associated with life-threatening arrhythmias. Several studies have shown that panic disorder is associated with an increased sensitivity to yohimbine and a blunted growth hormone response to clonidine, which are alpha-2 adrenoceptor antagonist and agonist, respectively. This study investigated the changes in QTvi (QT variance corrected for mean QT interval squared/HR variance corrected for mean HR squared) during placebo, oral clonidine (150 mg) and oral yohimbine (20 mg) in a double-blind design in 12 normal controls and 19 patients with panic disorder. HR and QT variability measures, especially QTvi, were obtained before and after the administration of these drugs to patients in supine and standing postures. As expected, patients with panic disorder became more anxious after yohimbine. In addition, the patients had a significant increase in QTvi after yohimbine and a significant decrease in QTvi after clonidine, which was not seen in the control group. The decreased anxiety after placebo was associated with decreased QTvi in patients. This study supports the previous reports of an abnormal sensitivity of alpha-2 adrenergic receptors in patients with panic disorder compared to controls and partly explains the association of increased cardiovascular mortality with conditions of anxiety. QTvi, a non-invasive indicator of cardiac repolarization lability, appears to be a useful tool to study cardiac sympathetic function.