Depressed patients (unipolar) were given one of the following combinations in an attempt to test aspects of the 'amine hypothesis' and to find a preferential therapy: (1) clomipramine; (2) clomipramine and tryptophan; (3) desipramine and clomipramine, and (4) desipramine and tryptophan. Treatment (2) should have given optimal potentiation of 5-HT neurones and (3) and (4) should have acted similarly on both serotoninergic and adrenergic pathways. In no group was there any evidence of accelerated recovery, indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis.