OBJECTIVE: The goal of the study described here was to evaluate interictal heart rate variability (HRV) in young patients with epilepsy, a patient population in whom sudden unexpected death in epilepsy (SUDEP) is known to be more common. METHODS: Twenty-four-hour ambulatory ECG Holter recordings of 37 patients (15-40 years old) and 32 healthy controls were compared. RESULTS: All of the time domain indices (SDNN, SDANN, RMSSD, and HRV triangular index) were significantly suppressed (P<0.001), and there was a marked reduction in parasympathetic tone (reduced HF(nu,)P<0.001) and an increase in sympathetic tone (increased LF(nu) and LF/HF ratio, P<0.001) in the patient group. Stepwise linear regression analysis revealed that polytherapy and epilepsy duration >10 years were independent variables associated with a reduction in SDNN. CONCLUSION: Our data suggest that the major determinants of suppressed SDNN are polytherapy and epilepsy duration >10 years. Analysis of spectral measures of frequency domain indices suggests that an increased sympathetic tone in association with a decreased parasympathetic tone may constitute the mechanism underlying SUDEP in young people with epilepsy.