BACKGROUND AND AIM: Studies have shown that altered visceral perception and lower pain thresholds in patients with symptomatic gastroesophageal reflux disease (GERD) and non-cardiac chest pain. Autonomic changes associated with the perception of heartburn in patients with GERD are poorly understood. METHODS: A total of 12 GERD patients (six male, six female; mean age 37.2 +/- 2.7 years) and 12 controls (five male, seven female; mean age 32.8 +/- 2.2 years) were studied. The study protocol included a 20-min water infusion (6 mL/min), and 20-min acid infusion (0.1 N HCl, 6 mL/min). Spectral analysis of heart-rate variability (HRV) was used to assess autonomic functioning. The measured HRV indices included the power in the low-frequency (LF) band (0.04-0.15 Hz) reflecting sympathetic tone, and power in the high-frequency (HF) band (0.15-0.5 Hz) reflecting vagal tone, and the LF/HF ratio as an indicator of sympathovagal balance. RESULTS: The GERD group experienced more heartburn than controls with acid infusion. Between-group comparisons showed no significant changes in LF band power in any period. The HF band power was significantly lower in GERD patients during all infusion periods. The LF/HF ratio was significantly larger in GERD patients. CONCLUSIONS: The perception of heartburn induced by esophageal acid infusion is associated with a simultaneous increase in sympathetic modulation in patients with GERD. The autonomic responses with esophageal acid infusion are significantly different between healthy subjects and GERD patients.