The profound reduction in heart rate variability (HRV) that occurs during exercise is thought to be, at least in part, the result of sympathetic nervous system activation. Moxonidine is a centrally acting anti-sympathetic drug, which suppresses sympathetic nervous system outflow by stimulation of central imidazoline receptors located in the rostral ventro-lateral medulla. This study was designed to investigate the combined effects of central sympathetic inhibition with moxonidine and steady-dynamic exercise on HRV. Ten normal males participated in a double-blind cross-over study, taking either placebo or 0.4 mg of moxonidine. The subjects were studied at rest and during steady-state exercise. HRV was measured considering both time and frequency domain parameters. As a non-linear measure, the Poincaré scatter-plot was measured and analysed quantitatively. Ventilation and gas exchange were also measured during exercise. In addition, plasma catecholamines were measured at rest and during exercise. The only parameter changed, at rest, by moxonidine was the blood pressure which was reduced. During exercise, moxonidine reduced plasma noradrenaline (NA), compared with the placebo (P<0.01). The only change observed in HRV during exercise was a significant reduction of the continuous long-term standard deviation (SD2) of the Poincaré scatter-plot of the R-R interval (P<0.05). However, the potential and prognostic significance of this result needs to be further assessed.