3 and a fraction mayor may not respond to treatment. On the behavioral level, animal research shows that a variety of experimental conditions can induce de pression. The same is true in the field of treatment, where pharmacologically highly different drugs can equally alleviate depression in animals and hu mans. The question as to whether this is due to a heterogeneity of depressive subjects based on different pathogenetic mechanisms is open to discussion. We can look for common features of all possible causal factors in the hope of finding a single basic mechanism. Many divergent findings may also be ex plained as peripheral changes of a highly complicated dynamic system. In the field of psychopharmacology, a circular reasoning has become evident in the sense that originally the clinical antidepressive response was founded on empirical grounds only. In a second step, an attempt was made to characterize some clinically active compounds pharmacologically, and in a third, further compounds were developed based on aspects of the pharmaco logical profiles. Moreover, the post hoc development of a pharmacological screening method has the serious disadvantage of delaying breakthroughs into new fields.