<h3>Objective:</h3> To identify cerebral hemispheric lateralization in cardiac autonomic control. <h3>Patients:</h3> Eight patients undergoing an intracarotid amobarbital sodium test as a presurgical evaluation of temporal lobe epilepsy. <h3>Design:</h3> Power spectral analysis of heart rate variability before and after intracarotid amobarbital injection. <h3>Setting:</h3> University hospital and research center. <h3>Main Outcome Measure:</h3> The changes in the ratio of low-frequency (LF) (sympathetic) to high-frequency (HF) (parasympathetic) power (LF/HF ratio), a measure of sympathovagal balance, after hemispheric inactivation. <h3>Results:</h3> The LF/HF ratio changed as follows: right preinactivation=3.81±0.96, postinactivation=3.40±1.23; left preinactivation=2.74±0.49, postinactivation=4.34±0.59 (mean±SEM). The test of interaction between laterality and inactivation using a 2-way repeated-measures analysis of variance was statistically significant (<i>P</i>=.001). The increased ratio on the left side (1.61±0.70) was statistically significant (<i>P</i>=.03), but the decrease on the right side (−0.40±0.46) was not (<i>P</i>≤.70). <h3>Conclusions:</h3> These findings suggest that there is a cerebral lateralization in cardiac autonomic control and that the right cerebral hemisphere predominantly modulates sympathetic activity. This study may help identify subgroups of patients with intracranial disease at high risk of cardiac complications.