Pretreatment plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram, a selective serotonin uptake inhibitor, against maprotiline, a selective noradrenaline uptake inhibitor. The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls. Plasma Tyr ratio was normal in the endogenous, but significantly decreased in the non-endogenous depressives. There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF, or between the plasma Tyr ratio and HVA level in CSF, whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio. There was a significantly positive correlation between the Trp ratio, the Tyr ratio, their sum and the final Hamilton depression score in 14 patients treated with citalopram; on the whole, this association was evident also in the endogenous and non-endogenous subgroups. In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score; this association was poor in the endogenous, whereas a trend towards a correlation remained in the non-endogenous subgroup. The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline. However, further studies are needed on larger patient samples to allow a firm conclusion.