There are indications that the group of vital ('endogenous') depressions encompasses a subgroup with central 5-HT deficiency and that this factor contributes to the development of the (or some) depressive symptoms instead of resulting from them. In a majority of patients the suspected 5-HT deficiency persists even when the depressive symptoms have disappeared and the medication has been discontinued. This led us to the hypothesis that the disturbed central 5-HT metabolism is not a direct causal, but a predisposing factor. If this is true, then abolition of the suspected 5-HT deficiency, for example with the aid of 5-HTP, can be expected to have a prophylactic effect. This hypothesis was investigated in this study and confirmed. 5-HTP reduces the relapse rate in recurrent vital depressions with a unipolar and those with a bipolar course. This effect would seem to be most pronounced in patients whose disorders of central 5-HT metabolism are persistent. Tentatively it was concluded that 5-HTP seems to be inferior to lithium in bipolar patients and at least equivalent to lithium in unipolar patients. This problem, however, is still under investigation. 5-HTP prophylaxis is the first aimed (i.e. pathological substrate-oriented) type of chemoprophylaxis known in psychiatry.