To assess the status of serotonergic neurotransmission in depressed females, the authors examined the excretion of free cortisol in 24 h urine both before and after administering 5 g L-tryptophan (L-TRP) orally. The depressed patients were classified according to the DSM-I11 into minor, simple major and major depression with melancholia. We found a significant, enhancing effect for L-TRP on urinary free cortisol (UFC) excretion. The absolute increments in UFC induced by L-TRP were significantly higher in melancholic females as compared to minor and simple major depressives. We found no differences among the DSM-I11 groups in the availability of L-TRP to the brain, 9 h after L-TRP administration.