Deficient endogenous pain inhibition, e.g. Diffuse noxious inhibitory controls (DNIC), or hormonal abnormalities like hypocortisolism, could be responsible for chronic widespread pain in Chronic Fatigue Syndrome (CFS). Thirty-one CFS-patients with chronic pain and 31 healthy controls were subjected to spatial summation of thermal noxious stimuli by gradual immersion (ascending or descending) of the arm in warm water (46 degrees C). They rated pain intensity every 15s. Every immersion took 2 min, alternated with 5 min rest. Before and after immersion, salivary cortisol was assessed. Overall pain ratings were higher in CFS-patients, but the evolution was not different between patients and controls, during both ascending and descending immersion. Pain intensity and immersed surface were only correlated during the descending session in both patients (r=.334) and controls (r=.346). When comparing the first and the last 15s of every emersion, it was found that pain inhibition starts slower for CFS-patients in comparison to healthy subjects. Both pre- or post-values and cortisol response did not differ between controls and patients. The drop in cortisol was significantly correlated to pain intensity in CFS (r between .357 and .402). In addition to the hyperalgesia in CFS, DNIC react slower to spatial summation of thermal noxious stimuli. We found no evidence for hypocortisolism in CFS, and the cortisol response to nociception was not different in CFS compared to healthy subjects. In conclusion, delayed pain inhibition may play a role in chronic widespread pain in CFS but further research is required.