Glucocorticoids are major protectors during and after stress. Centrally, glucocorticoids counterbalance and regulate three neurochemical systems active during stress: the noradrenergic system, the serotonin system and the GABA benzodiazepin system. But glucocorticoids can compromise immune defence systems leading to nerve cell destruction in the hippocampus. Certain types of stress can also lead to loss of neurons in the hippocampus, one of the most stress susceptible regions. Tianeptine decreases morning hypersecretion of glucocorticoids induced by a contention (1 hour) stress. Moreover, tianeptine inhibits the decrease in the number of type I glucocorticoid receptors induced by isolation stress. Tianeptine inhibits the increase in the tryrosine hydroxylase messenger RNA, also induced by isolation stress. Finally, tianeptine tends to increase dendrite ramifications of the hippocampus' pyramidal neurons (CA3) in isolated rats, thus counteracting the effect of isolation stress. Because of the positive results obtained with tianeptine on the hypophyseal-adrenal gland function and on the hippocampus, the authors are persuing further investigations to determine whether tianeptine can inhibit the loss of hippocampus nerve cells induced by repeated glucocorticoid administration or repeated stress and whether it potentializes the beneficial effects of glucocorticoids on the noradrenergic, serotonin and GABA benzodiazepin systems.