The uptake of tryptophan and tyrosine by the brain has been studied in 6 manic-depressive patients and in 8 schizophrenics. In an attempt to saturate the blood-brain transport mechanisms, this uptake has been evaluated by measuring the arteriovenous differences (arterial plasma-internal jugular plasma) of these two amino acids before and after perfusion with Z,-dopa and L-5-HTP. Considering a positive difference as an uptake and a negative one as an outflow, results show (1) in melancholia an uptake of tryptophan and an outflow of tyrosine; (2) in mania an uptake of tyrosine and an outflow of tryptophan, and (3) in schizophrenia an outflow of tryptophan accompanied with either an uptake or an outflow of tyrosine. In addition, the kinetics of tryptophan binding to plasma proteins and the ratio of tryptophan/tyrosine uptake are different in manic-depressive illness and in schizophrenia. These results support the view that a disturbance in the blood-brain transport mechanisms of tryptophan and tyrosine could be involved in the physiopathology of manic-depressive illness and schizophrenia.