There is evidence that a functional deficit of serotonin/noradrenaline and/or of their precursors L-tryptophan (L-TRP)/tyrosine and disorders in the hypothalamic-pituitary-adrenal (HPA) axis are linked to the pathophysiology of severe depressions. Several reports suggest a reciprocal relationship between these neurotransmitters and HPA axis activity. In order to investigate the effect of glucocorticoid excess on the availability of L-TRP and tyrosine to the brain, we measured urinary cortisol (UC) excretion in 24-h urine, and the availability of both amino acids before and after treatment with 1 mg dexamethasone in 26 depressed patients. We found no relationship between UC excretion and the availability of either amino acid. Dexamethasone significantly suppressed the availability of L-TRP (P less than 10(-5] and of tyrosine (P = 0.005). Major depressed patients with melancholia exhibited a significantly lower availability of L-TRP than minor depressives (P = 0.007).