We have explored the possibility of using measures of 5-HT (extracellular 5-HT and 5-HIAA in blood) as peripheral indexes of MAO activity. Depressed patients treated with phenelzine for 6 weeks display a dramatic increase of plasma 5-HT (270% of basal values) together with a decrease of plasma 5-HIAA. After treatment with irreversible MAO inhibitors, rat plasma 5-HIAA decreased in a similar fashion than MAO-A activity in liver, lungs and brain, measured using 5-HT as substrate. These results support the use of plasma 5-HT and 5-HIAA in humans to evaluate the action of MAOI on the serotonergic system.