OBJECTIVE: Heart rate variability (HRV) reflects the balance of activities of sympathetic and parasympathetic components of the autonomic nervous system. We compared HRV parameters in response to a prolonged fast in obese versus normal weight humans. In addition, the effect of weight-loss was evaluated in obese individuals. DESIGN: Intervention study. PATIENTS: The study subjects included 14 nondiabetic obese (12 females/2 males, aged 30 +/- 3 years, Body Mass Index (BMI) 35.2 +/- 1.2 kg/m(2) ) and 12 lean subjects (10 females/2 males, aged 27 +/- 3 years, BMI 23.3 +/- 0.5 kg/m(2) ). MEASUREMENTS: HRV was examined 75 min after standardized breakfast and after a 48-h fast in 14 nondiabetic obese and 12 lean subjects. The postprandial measurement was repeated in 12 obese subjects after weight-loss. RESULTS: In lean subjects, fasting decreased high-frequency (HF) power by 43% (P < 0.05) and decreased low-frequency (LF) power by 37% (P = 0.1), leaving the LF/HF ratio unchanged (P = 0.7). In the obese group, autonomic nervous system tone shifted to sympathetic dominance as the LF/HF increased from 0.61 to 1.14 (P = 0.03). After an average weight-loss of 13.8 kg in obese subjects, a trend for sympathetic dominance was found; the LF/HF ratio increased by 56% (P = 0.06). CONCLUSION: Our data show that a 48-h fast leaves autonomic nervous system balance unaltered in lean subjects. In contrast, a 48-h fast, as well as weight-loss, induces sympathetic dominance in obese humans.