Heart rate is physiologically controlled by adaptive changes in sympathetic and parasympathetic tone. While it is evident from earlier studies, that activation of b₁-adrenergic receptors is a major mechanism to induce tachycardia in mice, the relevance of b₁-adrenergic signalling for heart rate regulation at low heart rate levels and its relation to physical activity is unknown. To address this question, telemetric ECG devices (D.S.I.) were implanted in male mice (n=7, 32±1 g), and heart rate as well as physical activity were recorded under control conditions and during increasing doses of the selective b₁-adrenoceptor antagonist metoprolol (per os, 30, 90 and 270 mg/kg per day). Metoprolol had only modest bradycardic effects during day time (-17±10, -26±8, and - 18±12 bpm), whereas it caused much more pronounced and dose-dependent reductions of heart rate during night time (-28±14, -40±13 and -60±14 bpm). To dissect the circadian effects from those of physical activity, heart rate responses were normalized to activity. During periods without physical activity (sleep or rest), metoprolol had only a minimal bradycardic effect, which was identical during day and night. The efficacy of metoprolol to reduce heart rate increased directly with increasing levels of physical activity; at the highest activity level, metoprolol reduced heart rates by ~30%. The level of physical activity was not affected by metoprolol. In summary, these data show that a significant, but modest adrenergic tone is present in resting unrestrained mice. The adrenergic influence on heart rate steeply increases with physical activity. The dose of metopolol required to reduce heart rate is considerably higher in mice than in humans.