Objective: To compare salivary, plasma and urinary free cortisol (UFC) measurements in patients with anorexia nervosa, in whom an overdrive of the hypothalamic±pituitary±adrenal (HPA) axis is well established but information on salivary cortisol is lacking, in viscerally obese patients in whom subtle abnormalities of cortisol secretion and metabolism are postulated, and in normal-weight healthy women. Participants and experimental design: Measurement of salivary cortisol offers a convenient way to assess the concentrations of free, biologically active cortisol in plasma in different physiopathological settings. Forty-seven drug-free, newly diagnosed women with active restrictive anorexia nervosa, 30 restrictive anorexic women undergoing chronic psychopharmacological treatment, 47 women with mild-to-moderate visceral obesity, 103 women with severe central obesity and 63 normal-weight healthy women entered the study. Salivary and blood samples were collected at 0800 h, 1700 h and 2400 h, together with three consecutive 24-h urine specimens for UFC determination. In controls and patients with anorexia nervosa n 83Y salivary and plasma cortisol were also measured after a 1-mg overnight dexamethasone suppression test (DST). In patients with anorexia nervosa, mood was rated by the Hamilton scale for anxiety and depression. Results: Untreated patients with anorexia nervosa showed increased plasma and salivary cortisol and UFC concentrations (all P , 0X001 compared with controls), and decreased cortisol suppression after DST in plasma and saliva (P , 0X0001 and P , 0X005 respectively compared with controls). These alterations were less pronounced, although still statistically signi®cant, in treated patients with anorexia nervosa. Salivary cortisol was highly correlated with paired plasma cortisol in the whole population and after splitting the participants by group P , 0X0001X However, for plasma cortisol values greater than 500 nmol/l (the corticosteroid-binding globulin saturation point), this parallelism was lost. Taking plasma cortisol as a reference, the level of agreement for postdexamethasone salivary and plasma cortisol was 58.9% among suppressors and 77.8% among nonsuppressors (x 2 test: P , 0X01). Decreased 0800 h/2400 h cortisol ratios were observed in plasma and saliva in drug-free patients with anorexia nervosa (P , 0X005 and P , 0X05 respectively compared with controls), and in saliva in severely obese patients (P , 0X05 compared with controls). Depression and anxiety scores were unrelated to cortisol concentrations in any compartment. Conclusions: Salivary cortisol measurement is a valuable and convenient alternative to plasma cortisol measurement. It enables demonstration of the overdrive of the HPA axis in anorexia nervosa and subtle perturbations of the cortisol diurnal rhythm in women with visceral obesity. With the establishment of more speci®c and widely acceptable cut-off values for dynamic testing, measurement of salivary cortisol could largely replace plasma cortisol measurement.