Objective Circulating endotoxin impairs the sympathetic regulation of the cardiovascular system in animals. We studied the changes in the autonomic control of the heart and circulation during septic shock in humans. Design 12 patients (age 43.0±6, 17–83 years) were investigated during septic shock (mean duration: 3.5±0.5 days) and during recovery, fluctuations in R-R interval, invasive arterial pressure (AP) and peripheral arteriolar circulation (PC, photoplethysmography) were evaluated by spectral analysis as a validated nonivasive measure of sympathovagal tone. Apache II score was adopted as the disease severity index. Low frequency components (0.03–0.15 Hz) of the frequency spectra were expressed as relative to the overall variability (LFnu) for each cardiovascular variable. Results LFnu were low or absent during shock but, in the 10 patients who recovered, increased by the time of discharge (post-shock). R-R LFnu increased from 17±6 to 47±9 (p