The effects of the novel antidepressant tianeptine, after acute or chronic administration, were compared in normal and restraint-stressed (30 min or 2 h) Wistar rats. Tianeptine, at the dose of 10 mg/kg, did not exert any effect in non-stressed rats. However, in animals restrained for 30 min, tianeptine reduced the increase of circulating ACTH and β-endorphin levels without modification of corticosterone. Moreover, it antagonized the deficit of vertical exploratory activity in an open field. In rats restrained for 2 hours, a single injection of tianeptine suppressed the stress-induced increase of TAT hepatic activity and moderately attenuated the deficit of activity in the open field. This effect was less marked and not statistically significant after chronic treatment.