The plasma ratio of each neutral amino acid (tryptophan (TRP), tyrosine (TYR), valine, isoleucine, leucine (LEU) or phenylalanine) to the sum of the other neutral amino acids was measured in 16 manic and 14 depressed patients. In the manics, there was a correlation between the psychomotor activity and the plasma TRP and LEU ratios. In the depressives, the depressed mood, retardation and global severity were correlated with the TRP ratio. The zotepine responders showed an increase in the TRP ratio after treatment. In the mianserin responders, the TYR ratio, which was high before the treatment, decreased to the normal range after the treatment. But, the plasma amino acid ratios remained unchanged in the patients treated with lithium carbonate or amitriptyline. These results suggest that, in manic-depressive illness, there might be abnormalities in the metabolism of neutral amino acids, mainly of TRP and TYR, and that the plasma TRP and TYR ratios might be important indicators for determining the efficacy of some drugs.