In order to investigate possible disturbances of the blood-brain transport mechanisms of monoamine precursors in manic-depressive illness and schizophrenia, we have measured the brain arterio-venous difference of DOPA, or 5-HTP, or tyrosine and tryptophan in 36 patients, during the infusion of either L-DOPA or L-5-HTP. The infusion lasted for 30 min, and blood was sampled during and immediately after the infusion, simultaneously in the femoral artery, the jugular vein and a vein of the arm. During the infusion of L-DOPA, manic patients have a higher extraction of L-DOPA than depressive patients and controls. During the infusion of L-5-HTP, pdpressive patients have a higher brain extraction of 5-HTP than manic or schizophrenic patients. In depressive patients, a small uptake of tryptophan correlated with a large outflow of tyrosine was observed. The opposite was seen in manic patients, with an outflow of tryptophan correlated with an uptake of tyrosine. In schizophrenics, there was an outflow of tryptophan and random variations of tyrosine. These brain arterio-venous differences were not correlated with arterio-venous differences for peripheral tissues. Taken together, these results are compatible with a disturbance of the blood-brain transport of amino acids precursors of monoamines in manic-depressive illness and schizophrenia.