BACKGROUND Analysis of heart rate variability (HRV) is a powerful method of assessing severity of conditions affecting the autonomic nervous system. OBJECTIVE To determine if HRV is decreased and if HRV reflects severity in COPD. METHODS Prospective determination of HRV from 24-h outpatient Holter recordings. METHODS Eighteen individuals with PiZ alpha1-antitrypsin deficiency: 13 with COPD and 5 with normal FEV1. HRV was also determined in 18 matched normal control subjects. Approximately 3 years after the initial recording, all COPD subjects were contacted to determine current status. METHODS Indexes of heart rate (HR) and HRV were compared for groups of patients with and without COPD and their control subjects. RESULTS Mean and minimum HRs were higher in COPD patients. Virtually all indexes of HRV were significantly decreased in COPD patients. No differences were found in HR or HRV between PiZ individuals with normal FEV1 and their age-and gender-matched control subjects. Patients who had a change in status (ie, death, lung transplant, listed for transplant) had significantly higher daytime HRs, lower values for HRV indexes reflecting mixed sympathetic and parasympathetic modulation of HR, and reduced daytime high-frequency spectral power, an index of cardiac vagal modulation. Significant correlations (r=0.48 to 0.88) were found between FEV1 and these and other indexes of HRV. Most other indexes of HRV also tended to be lower for the group whose status had changed. CONCLUSIONS PiZ alpha1-antitrypsin deficiency COPD is associated with abnormal cardiac autonomic modulation. Indexes of HRV appear to reflect severity and may have prognostic value in COPD patients.