Objectives: To evaluate whether heart rate variability (HRV) can be used as an index of parasympathetic reactivation following exercise. Background: Heart rate recovery post-exercise has recently been shown to have prognostic significance, postulated to be related to abnormal recovery of parasympathetic tone. Methods: Ten normal subjects (5 male, age 33±5 years) exercised to their maximum capacity and 12 subjects (10 male, age 61±10 years) with coronary artery disease exercised for 16 minutes on 2 separate occasions, once in the absence of atropine and once with atropine (0.04 mg/kg) administered during exercise. The root-mean-square residual (RMS), which measures the deviation of the RR intervals from a straight line, as well as SD and MSSD were measured on successive 15, 30, and 60-second segments of a 5-minute ECG obtained immediately following exercise. Results: In recovery, the RR interval was shorter with atropine (p<0.0001). Without atropine, HRV, as measured by the MSSD and RMS, increased early in recovery from 4.0 ± 0.4 msec and 3.7 ± 0.4 msec in the first 15 seconds to 7.2 ± 1.0 msec and 7.4 ± 0.9 msec after one minute, respectively. (p<0.0001). RMS and MSSD were less with atropine (p<0.0001). RMS (range 1.7-2.1 msec) remained flat throughout recovery while MSSD showed some decline over time from 3.0 to 2.2 msec (p<0.002). RMS and MSSD were both directly related (R² = 0.47 and 0.56, respectively, p<0.0001) to parasympathetic effect, defined as the difference in RR interval without and with atropine. Conclusion: RMS and MSSD are parameters of HRV that can be used in the post-exercise recovery period as indices of parasympathetic reactivation following exercise. These tools may improve our understanding of parasympathetic reactivation following exercise and the prognostic significance of heart rate recovery.