Using spectral analysis of heart rate, several studies have shown that panic disorder patients are characterized by a reduced heart rate variability (HRV), indicative of abnormalities in autonomous nervous system (ANS) function. We recently reported that patients with panic disorder, who did not respond to pharmacotherapy, were characterized at baseline by a higher heart rate. In this study, ANS functioning is investigated as a possible predictor of nonresponse to pharmacotherapy. Twenty-eight medication-free panic disorder patients entered a 12-week open-label treatment study with mirtazapine. Five-minute HRV recordings were obtained before treatment and were analysed using spectral analysis. The data of 17 patients could be used. The total spectrum and low frequency power of responders to mirtazapine were significantly higher than those of nonresponders. Our findings suggest that nonresponders to short-term mirtazapine treatment are characterized at baseline by a lowered output of the ANS. The results are preliminary in view of the small sample studied.