Five healthy female subjects participated in a starvation experiment. After an initial baseline phase (A) they lost about 8 kg in a 3-week phase of complete food abstinence (B); thereafter they recovered to their original body weight (C) and kept this weight stable over more than 4 weeks (D). While all dexamethasone suppression tests (DST's) during the initial baseline were normal, half of the DST's (7/14) in the fasting phase showed insufficient suppression. In the following weight gain phase, all DST's were sufficiently suppressed. Twenty-four hour plasma cortisol patterns during fasting (B) showed a significant increase, as well as increased cortisol half-life, increased time in secretory activity, and increased number of secretory episodes. Administration of the alpha 2-adrenergic receptor agonist clonidine during fasting did not induce a further decrease in plasma cortisol level, whereas it did during baseline. The results demonstrate that weight loss, reduced caloric intake, and catabolic state have a very powerful influence on the hypothalamo-pituitary-adrenal (HPA) axis and other endocrine systems. The results shed new light on endocrine dysfunctions in mental disorders associated with reduced caloric intake, such as anorexia nervosa and depression, and question the specificity of certain endocrine dysfunctions for depression.