The effect of tricyclic antidepressant treatment on basal thyroid hormone levels was evaluated in 28 subjects with primary major depression. In the total group, tricyclic antidepressant treatment was associated with significant reductions in measures of thyroxine. Furthermore, responders to antidepressant treatment had significantly greater decrements in thyroxine and the free thyroxine index as compared with nonresponders. This finding appears consistent with the effects of a wide range of antidepressant treatments on thyroid function tests.