We have studied the effect of amitriptyline, a tricyclic anti-depressant drug on several immune parameters of the Balb/c mice in order to evaluate its immunomodulatory effects. Results showed that amitriptyline will potentiates all of the immunocytes functions except for the production of PGE2 by LPS stimulated monocytes. We have also showed that amitriptyline can normalize the immunosuppressive effect of dexamethasone on mice (experimental stress). These results suggest that one of the mechanisms of action of the tricyclic anti-depressant drugs might be through the modulation of the immune system which has been suppressed by stress or distress