Growing evidence suggests that alterations in autonomic function contribute to the pathophysiology of panic disorder (PD). This retrospective study employed 24-h heart rate variability (HRV) analysis of Holter records to compare autonomic function in PD patients (n = 38) with healthy, age- and gender-matched controls. Both time and frequency domain measures were calculated, and a circadian rhythm analysis was performed. The SDNN index, 5-min total power, very low frequency (VLF) and low frequency (LF) power were significantly lower in panic patients relative to controls over the 24-h period. Hourly means were significantly lower during some of the waking hours as well as the latter part of the sleep cycle. In contrast, the mean RR interval, RMSSD and high frequency (HF) power were comparable in patients and controls. Results suggest that sympathetic activity is depressed in PD patients under usual life conditions, leading to a relative predominance of vagal tone. Findings of low HRV in PD patients are consistent with the high rate of cardiovascular morbidity and mortality in this population, as well as with the emerging view of panic as a disorder involving reduced flexibility and adaptability across biological, affective and behavioral dimensions.