ST segment depression frequently is observed in women undergoing cesarean section with regional anesthesia, yet myocardial ischemia as a cause of such depression seems unlikely in this healthy population. To test whether ST segment depression in this setting is due to decreased sympathetic outflow to the heart, we monitored electrocardiograph (ECG) leads II and V5 in 15 healthy women undergoing cesarean section with spinal anesthesia. We estimated cardiac sympathetic tone by spectral analysis of heart rate variability, measuring the area under the power•frequency curve of the fast Fourier transform of heart beat intervals. The area under this curve in the low frequency range (0.02-0.15 Hz) has been described recently and validated in humans and animals as a semiquantitative measure of cardiac sympathetic tone. Significant, > 1 mm horizontal or downsloping depression of the ST segment occurred in five women (33%), beginning 5-30 min after spinal bupivacaine injection. Those with ST segment depression had increased heart rate (117 ± 7 beats/min) compared to those without (94 ± 6 beats/min; P < 0.05), and had received more ephedrine (25 ± 3 mg vs 7 ± 3 mg; P < 0.05). Before spinal bupivacaine injection and after block resolution the area in the low frequency range of the heart rate power spectrum was similar in all women. During spinal anesthesia, those with ST segment depression had less power in this low frequency range (0.0018 ± 0.0010 ms2/Hz) than those without ST depression (0.0028 ± 0.0006 ms2/Hz). Despite similar levels of sensory block to pin testing (median T3), these data suggest that the density of cardiac sympathetic block varies considerably during high spinal anesthesia. We propose that ST segment depression during cesarean section with regional anesthesia is most often due to diminished cardiac sympathetic tone, likely with differing densities of right and left cardiac sympathetic neural block. Inasmuch as myocardial ischemia causes an increase, not decrease in cardiac sympathetic tone as determined by spectral analysis of heart rate, these data provide confirming evidence that ST segment depression during cesarean section is not due to myocardial ischemia.