The last decade of psychopharmacological research in depression is characterised by the development of structurally novel and biochemically selective-acting drugs and by the shift of interest from the acute to long-term treatment effects of antidepressants on catecholaminergic transmission. Of particular importance in this respect are the findings demonstrating adaptative changes occurring at receptor levels which have led to alternative theoretical formulations about the origin of depression and the mode of action of antidepressants. However in spite of the progress in this field of research the mechanism of therapeutic action of antidepressants remains unknown. Examples of drugs not affecting NA and 5-HT uptake or release and producing no adaptative changes of adrenergic receptors (trimipramine, levoxaprotiline) indicate that antidepressant-like activity can be achieved by mechanisms which still remain to be elucidated.