A depressed heart rate variability (HRV) is related to poor prognosis in septic multiple organ dysfunction syndrome (MODS). The role of endotoxin in the development of HRV reduction was evaluated by telemetrical ECG-recordings in freely roaming mice. Prior, the stabilisation period after operative ECG-transmitter implantation and the autonomic tonus in mice had been assessed. The heart rate, the HRV and circadian patterns normalize within 10 days. Autonomic regulation of resting heart rate is balanced. HRV is predominately parasympathetically mediated. Endotoxin causes instantaneous tachycardia; while administrated under autonomic blockade it induces pronounced bradycardia. The HRV is immediately depressed. The results functionally validate the previously reported direct interaction of endotoxin and the If-current. Thus, endotoxin in-vitro sensitizes If for sympathetic activation, and simultaneously inhibits channel activity. Both effects may contribute to the depressed HRV in MODS.