OBJECTIVE: To explore the effects of levodopa on heart rate variability (HRV) in Parkinson\'s disease (PD). METHODS: A total of 48 PD patients (M:F = 35: 13, mean age: 59 +/- 6 years, duration of illness: 4.7 +/- 1.8 years, Hoehn & Yahr stage: 2.2 +/- 0.3) on a stable dose of levodopa were recruited from January 2012 to May 2014.For confirming autonomic dysfunction, the baseline patient data (12 hours off-medication) were compared with a control group consisting of 48 age and gender-matched healthy subjects (M: F = 35: 13, mean age 58 +/- 6 years). Resting lead II electrocardiogram (ECG) was recorded at baseline and continuously after two tablets of 100/10 mg levodopa/carbidopa.However, 5-min segments were selected from every quarter, i.e., Q1 (0-15 min), Q2 (15-30 min), Q3 (30-45 min) and Q4 (45-60 min). Artifact-free 5-min segments of ECG were analyzed offline to acquire the parameters of heart rate variability in time and frequency domains. RESULTS: At baseline, PD patients had a significantly reduced standard deviation of normal-to-normal intervals (SDRR) [(24 +/- 4) vs (26 +/- 4) ms, P < 0.01)] and total power (TP) [(569 +/- 180) vs (652 +/- 205) ms(2), P < 0.05] when compared to controls. Comparing of HRV in PD patients at baseline and during first hour after drug administration, we observed significant increase in SDRR [(29 +/- 12) vs (24 +/- 8) ms, P < 0.05)], TP [(708 +/- 253) vs (569 +/- 180) ms(2), P < 0.01], low frequency power (LF) [(203 +/- 98) vs (168 +/- 60) ms(2), P < 0.05) ] and high frequency power (HF) [158 +/- 86) vs (114 +/- 90) ms(2), P < 0.05] in Q3. CONCLUSION: The results suggest an improvement in the overall variability of heart rate resulting from an enhanced vagal tone.