In order to investigate the relationships between the hypothalamic-pituitary-adrenal (HPA)-axis activity, the central serotonergic neurotransmission, and the peripheral metabolism of l-tryptophan (L-TRP), the authors measured the following: the postdexamethasone cortisol values, the cortisol responses to 125 mg 5-hydroxy-L-tryptophan (L-5-HTP) orally, and the total L-TRP/competing amino acids (CAA) ratio in 64 depressed females. Severely depressed females showed significantly lower values for L-TRP/CAA, significantly higher postdexamethasone cortisol values, and cortisol responses to L-5-HTP as compared with minor depressives. Dexamethasone nonsuppressors showed significantly lower L-TRP/CAA values as compared with suppressors. The cortisol responses to dexamethasone were significantly and negatively correlated with the availability of L-TRP. The cortisol responses to L-5-HTP were not related to either the availability of L-TRP or to the postdexamethasone cortisol values.