We have examined the effects of a single 12.5 mg dose and of 12 weeks treatment up to 37.5 mg daily with tianeptine, a new antidepressant drug that potentiates in vivo the uptake of serotonin (5-HT). On day 0, tianeptine reduced plasma 5-HT concentration. This acute effect occurred also on subsequent examination days. However, long-term treatment tended (P < 0.06) to increase basal plasma 5-HT concentrations, in covariation with decreases of MADRS (Montgomery-Asberg Depression Rating Scale) and HARS (Hamilton Anxiety Rating Scale). Platelet 5-HT increased only in elderly patients, probably due to the higher plasma concentration of the drug in this group than in younger patients. These results show that the acute effects of therapeutic doses of tianeptine are consistent with an enhancement of the 5-HT uptake. However, long-term treatment does not result in a decreased plasma 5-HT, as might be expected from the acute effects of the drug.