Hormone replacement therapy is universally associated with coronary heart disease (CHD) in observational studies, but it is unknown whether this association is mediated by the autonomic nervous system. We tested the hypothesis that postmenopausal hormone replacement therapy was associated with more favorable heart rate (HR) and heart rate variability (HRV) in a population sample of women (n=2,621). Hormone therapy use was measured at four examinations beginning in 1987. Supine HR and HRV indices were measured for 6 minutes at the final examination (1996-1998). In unadjusted linear regression models, hormone therapy was associated with lower HR (hormone use=64.7 vs. never=65.7 beats/min, P=.01) and higher HRV. However, following adjustment for age and CHD risk factors, both associations were eliminated. Results from this observational study suggest that hormone therapy is not associated with HR or HRV. These analyses should be replicated in a randomized trial.