Background: There is accumulating evidence of hypothalamic-pituitary-adrenal (HPA) axis disturbances in chronic fatigue syndrome (CFS). The salivary cortisol response to awakening hasbeen described recentlyas a non-invasive test of the capacityof the HP Aaxis to respond to stress. The results of this test correlate closely with those of more invasivedynamic tests reported in the literature; furthermore, i tcan be undertaken in a naturalistic setting.Aims: To assess the HPA axis using the salivary cortisol response to awakening in CFS.Method: We measured salivary cortisol upon awakening and 10, 20, 30 and 60 min afterwards in 56 patients with CFS and 35 healthy volunteers.Results: Patients had a lower cortisol response to awakening, measured by the area under the curve.Conclusions: This naturalistic test of the HPA axis response to stress showed impaired HPA axis function in CFS.</p