A clinical study with 361 female rats was conducted to elucidate the mechanism whereby MPA (medroxyprogesterone acetate) lowers 5-HT/5-HIAA ratio in the brain area and the possible role of serotoniergic mechanisms. In addition, the participation of MAO (monoamino oxidase) system and the effects of some steroids were studied in order to establish a relationship between chemical structure and activity. The effects of the following steroids were studied: MPA (medroxyprogesterone acetate), melengestrol acetate, chlormadinone, pregnenolone, -methyl pregnenolone, DOCA, acetoxi-progesterone, and ACTH (synacthen). Effects of these substances on LTP (liver tryptophan pyrrolase) activity, total and free plasma and brain stem Trp (tryptophan), and the 5HT and 5HTAA content in brain stem are tabulated. Of all the substances, only MPA and melengestrol acetate significantly raised LTP activity and both also lowered 5-HT content of brain stem. The high levels of ACTH in the blood of the adrenalectomized rats, as in those under fasting conditions, antagonized MPA effects. To further test this seeming result, ACTH and ACTH-MPA were injected into another group of animals. The ACTH not only increased plasma corticosterone but also antagonized the effect of MPA on the 5-HT content of brain stem. The study did not identify a relationship between chemical structure of the steroids studied and effects observed.