The amount of tryptophan (Trp) available for transport from plasma into the brain was estimated in patients with major depression before treatment for 4 weeks with a 5-HT potentiating tricyclic antidepressant (TCA), amitriptyline (n = 21) or clomipramine (n = 17), or a selective 5-HT uptake inhibitor, citalopram (n = 14) or paroxetine (n = 27). The ratio in plasma of Trp to the sum of the other large neutral amino acids (LNAA) was significantly inversely correlated with improvement on TCA, and patients with ratio Trp/LNAA below the mean improved significantly more than patients with a higher ratio but with comparable serum steady-state drug levels. The Trp concentration was a bit stronger inversely correlated with improvement on 5-HT uptake inhibitors than the ratio Trp/LNAA, and patients with Trp level below the mean improved significantly more than those with a higher level but with comparable serum steady-state drug levels. Plasma amino acid variables may be a useful tool for increasing the efficacy of antidepressant treatment.