Regarding the neurochemical pathogenesis of affective disorders a strict discrimination between pathogenetic, phenomenological and epiphenomenological neurochemistry has to be made. The possible functional role of an opioid-deficiency in the pathogenesis of endogenous depression and the therapeutic effect of recently developed opioid compounds are considered. Furthermore, the clinical use and the theoretical background of mood stabilizers in affective disorders and especially the mode of action of valproate is represented. As to the basic neurobiological factors regulating mood in normals and in patients with affective disorders an "unidimensional" model is confronted with a "bidimensional" scheme in which two different "gating-zones" are proposed. Interestingly, a neurochemical/psychopharmacological consideration of such a model reveals a new synopsis about the mode of action of psychoactive compounds modifying mood in patients with affective disorders.