The purpose of this study was to determine whether chronic fatigue syndrome (CFS) patients show autonomic dysfunction at the cardiac level and if so, to discover whether these abnormalities explain the fatiguability and/or other symptoms in CFS. The study population consisted of 21 CFS patients (Centers for Disease Control and Prevention [CDC] criteria, 1988) and 13 age- and sex-matched healthy controls. The autonomic testing consisted of: (1) postural challenge: registration of heart rate and blood pressure (BP) and heart rate variability in supine and in upright position (tilted to 70 degrees); (2) Valsalva maneuver; (3) handgrip test; (4) cold pressor test; and (5) heart rate response to deep breathing. Statistical analysis was performed using the Mann Whitney rank sum test; results of the test were considered significant at the 0.05 level. After tilting heart rate was significantly higher in CFS patients compared with healthy controls (mean CFS = 88.9 beats/min vs control = 77.9 beats/min; P <0.01). Low frequency power after tilting was significantly higher in CFS patients compared with controls (mean CFS = 0.603 vs control = 0.428; P = 0.02). There was a trend toward an increased heart rate during the cold pressor test. Other parameters did not differ between the CFS and control populations. The observed changes point toward a sympathetic overactivity in CFS patients when they are exposed to stress. Parasympathetic abnormalities could not be observed. Therefore, our findings provide no real explanation for the fatigue and intolerance to physical exertion in these patients.