We tested the hypotheses that the heart rate (HR) response to muscle metaboreflex activation induced by postexercise muscle ischemia (PEMI) varies considerably among subjects and that individual differences in the HR response are associated with differences in cardiac autonomic tone and/or arterial baroreflex function during PEMI. Fifty-one healthy subjects (36 men and 15 women) performed a 1-min isometric handgrip exercise at 50% maximal voluntary contraction, which was followed by a 3.5-min period of imposed PEMI. We estimated cardiac autonomic tone using spectral analysis of beat-to-beat variation in the R-R interval (RRI). In addition, the sensitivity of the arterial baroreflex control of HR (BRS) was evaluated using transfer function analysis of systolic arterial pressure (SAP) and RRI. Although the mean RRI during the PEMI and subsequent recovery period did not differ from the resting value, the variance among the individual differences in RRI between the rest and PEMI periods was significantly greater than between the rest and recovery periods. The changes in RRI elicited by PEMI correlated significantly with changes in the spectral power of the RRI variability in the high-frequency range and the BRS. By contrast, no significant correlation was observed between changes in RRI and changes in mean arterial pressure or the power of the RRI variability in the low-frequency range. This suggests that, in humans, the HR response to PEMI-induced activation of muscle metaboreflex varies considerably from individual to individual and that these differences reflect changes in cardiac parasympathetic tone and spontaneous BRS during PEMI.