The results of several clinical investigations have suggested that a special relationship exists between thyroid function and affective disorders and/or the therapeutic response to antidepressants. Animal studies have shown the possible beta-adrenergically mediated antidepressant-like properties of triiodothyroacetic acid (TRIAC) in rodents. The present experiment showed (1) that the reversal by antidepressants (clomipramine or imipramine) of escape deficits produced by previous exposure to uncontrollable shock was significantly hastened in animals given TRIAC and (2) that L-penbutolol treatment prevented the elimination of helpless behavior induced by TRIAC, suggesting a beta-adrenergic mediation of the antidepressant activity of thyroid compounds. The study confirmed that learned helplessness might be a useful model for studying in animals the neurohormonal correlates of affective disorders and the neurobiochemical basis of the enhancement of the antidepressant action produced by thyroid compounds.