Ventricular response (VR) during atrial fibrillation (AF) is a complex process, which is modulated by the autonomic nervous system (ANS). The purpose of this study was to characterize VR to both exercise as ANS stimulus and flecainide which is also supposed to have effects on the ANS. RR series were analyzed by means of time domain parameters and non-linear methods. In 15 patients (10 male, aged 55 plusmn 13 years) with persistent AF (mean AF duration 13 plusmn24 months), time domain parameters and indexes assessing the predictability of the time series, (regularity index, approximate entropy and an index for linear predictability) were evaluated. VR during exercise resulted modulated by adrenergic stimulation. Flecainide exhibited vagolytic activity especially during exercise. Thus, monitoring of exercise- induced and antiarrhythmic drug effects on ANS is possible with parameters derived from time domain and non-linear analysis.