Although heart-rate variability in the very-low-frequency (VLF) range of below 0.04Hz has been believed to derive from endocrine regulatory mechanisms including the renin-angiotensin- aldosterone system or thermoregulation, authentic mechanisms are not clear. We successfully explain how such heart-rate variability appears based on a hypothesis that heart rate is regulated by epinephrine from adrenal medulla, which is supported by the fact that VLF power shows circadian periodicity similar to that of the plasma adrenocorticotropic hormone stimulated by corticotropin-releasing factor. We demonstrated that VLF is a powerful biomarker to evaluate quality of sleep.