The present study was conducted in order to investigate the negative relationships between measures of hypothalamic-pituitary-adrenal (HPA)-axis activity and the availability of L-tryptophan (L-TRP) to the brain in depressive patients. To this end we measured the following: plasma total L-TRP, the ratio of L-TRP to the sum of competing amino acids (CAA), free urinary cortisol (UFC) excretion in 24 hr urine samples, and the 8 a.m. postdexamethasone cortisol levels. We found that the availability of L-TRP to the brain was significantly negatively correlated with the postdexamethasone cortisol values. Cortisol nonsuppressors averaged significantly lower L-TRP and L-TRP/CAA values compared to suppressors. No significant relationship was established between the availability of L-TRP and UFC excretion. It is concluded that the availability of L-TRP is related to the actual alterations in cortisol induced by dexamethasone rather than with the spontaneous baseline HPA-axis activity.