LM 5008, a potent 5-HT uptake inhibitor, induced an increase in plasma-free 5-HT level in a higher proportion than its metabolite 5-HIAA. In contrast, reserpine provoked a greater rise in 5-HIAA than in 5-HT, indicating stimulation of 5-HT turnover. LM 5008 potentiated the effects of reserpine on bound and free 5-HT and 5-HIAA levels but potentiated more the plasma-free 5-HT (4 times) than 5-HIAA (2.5 times), over reserpine-induced increases. Moreover, the rise in urinary excretion of 5-HT induced by reserpine was potentiated by LM 5008, whereas 5-HIAA was decreased. The differences between these two drugs implies that they do not act on the same platelet site. Since migraine has been proposed as a “low 5-HT syndrome,” LM 5008 may be useful as an anti-migrainous agent.