An altered autonomic balance is considered to be a pathogenetic factor in cluster headache syndrome, although there is varying data on sympathetic and/or parasympathetic activation during attacks and/or attack-free intervals. The aim of the present study was to evaluate the day/night pattern of heart rate during the active and remission phases of cluster headache. In addition, the relationship between heart rate changes and the site of pain was investigated to determine if an autonomic imbalance was related to the lateralization of pain. Thirty-nine patients (34 with primary episodic cluster headache and five with primary chronic cluster headache and 30 healthy controls underwent 24-h Holter ECG recording. Nine cluster headache patients were monitored during both phases of the disease. The data obtained confirmed the existence of a disordered chrono-organization in cluster headache (phase-shift of approximately 1 h of heart rate rhythm during the cluster period) together with a low heart rate variability and a higher occurrence of arrhythmias in cluster headache patients with right-sided pain. Differences were also observed in the cluster headache patients when headache free, excluding the pain itself as a reason for the abnormality. The chronobiological data point out a transient rhythmic dysfunction, while heart rate variability changes, mostly related either to the phase of the disease or to the site of pain, probably reflects a central, site-related, dysfunction of the autonomic nervous system in cluster headache.