Urinary 6-sulphatoxymelatonin (alpha MT6s) excretion was measured after one day and one, two and three weeks of desipramine treatment in eight depressed patients. There was significant increase in the urinary excretion of alpha MT6s after one week of treatment, and at no time was there any decrease in alpha MT6s excretion. These findings are opposed to the hypothesis that desipramine reduces noradrenergic neurotransmission in the human pineal. In a further five patients whose depression was resistant to desipramine alone, urinary alpha MT6s excretion was measured during treatment with adjunctive L-triiodothyronine (T3). There was no change in alpha MT6s excretion, and thus the previously reported potentiation of the efficacy of tricyclic antidepressants in combination with T3 does not appear to be mediated through an alteration in noradrenergic neurotransmission.