The discovery of the anti-depressive effects of imipramine and the MAO inhibitors, associated with the occasional depressions occurring during reserpine treatment was the starting point of modern research into depression. The concern with the neurochemical actions of these substances led to putting forth the noradrenaline and serotonin hypothesis of depression in the mid-60s. According to this, there is supposed to be a deficiency of noradrenaline and/or serotonin at the nerve endings in depression. This amine deficiency hypothesis has not been proved as yet in spite of intensive neurobiological research. Clinical as well as animal experiments in depressive patients with antidepressive drugs have led to the assumption that, in "endogenous" depression particularly, but also for the antidepressive mechanisms, alpha- and beta-adrenergic receptor changes play an important part.