The antidepressant mirtazapine has been demonstrated to acutely inhibit cortisol concentrations in healthy subjects and depressed patients. Since both depressed and anorectic patients are characterized by hyperactivity of the hypothalamo-pituitary-adrenocortical (HPA) system, the clinical usefulness and the endocrinological effects of mirtazapine were investigated in anorexia nervosa (AN). Five female patients suffering from AN restricting subtype (DSM-IV criteria) were admitted to a closed ward and treated with mirtazapine for three weeks receiving 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg mirtazapine per day from day 2 up to the end of the study (day 21). Besides weekly determination of clinical parameters (Body Mass Index [BMI], Hamilton Depression Rating Scale [21-HAMD]), salivary cortisol concentrations were measured before treatment (day - 1), at the beginning of treatment (day 0), after 1 week (day 7), and after 3 weeks (day 21) of treatment with mirtazapine. Saliva samples were collected hourly from 0800 up to 1,400 h. Repeated-measures ANOVA revealed a significant inhibition of salivary cortisol levels during 3-week treatment with mirtazapine (p<0.05) which became obvious already after the first mirtazapine administration (day 0). Moreover, a trend for an increase in BMI was seen (p=0.063), whereas no significant changes in 21-HAMD sum scores could be demonstrated. Double-blind, placebo-controlled studies are needed to clarify the question whether the observed changes in BMI are related to the mirtazapine-induced attenuation of HPA axis activity or whether they are due to monitoring of food intake and purgative behaviour on the closed ward.