Intraperitoneal or intracerebral injections of calcitonin in the rat produce several behavioral and hormonal effects which have some analogies with the human depressive syndrome. To determine if calcitonin effects are sensitive to antidepressant drugs, the ability of antidepressants and other psychotropic drugs to interact with calcitonin-induced anorexia was tested. The results show that chronic treatments (21 days) with tricyclic, or with tetracyclic, antidepressants significantly tend to neutralize the anorectic effect of calcitonin. Other antidepressants and other psychotropic drugs had no significant effect. The acute administration (24 h) of clomipramine did not antagonize the effect of calcitonin, and even significantly enhanced it. These results allow the author to propose the effects of calcitonin in the rat as a new animal model of depression, and to raise the hypothesis that a possible mechanism of action of tricyclic antidepressant treatments is to counteract the effects of certain brain peptides.