The effect of clonidine (0.05 mg/kg i.p.) on 5-hydroxytryptamine (5-HT) turnover has been studied in the whole brain and in various cerebral areas of the rat (brain stem, hypothalamus, striatum and "rest" of the brain). In the whole brain, clonidine produced a significant decrease (-23%) in 5-hydroxyindole acetic acid level and a slight increase (+7%) in 5-HT level. These variations were not observed in all the cerebral structures. The 5-hydroxyindole acetic acid levels were reduced in the hypothalamus and in the rest of the brain; they were not significantly altered in the brain stem and increased in the striatum. The effect of clonidine on the 5-HT synthesis has been studied by evaluation of the rises in 5-HT levels induced by pargyline: these rises were found significantly increased in the brain stem and the hypothalamus and not significantly altered in the other cerebral structures. These findings give support to the hypothesis according to which the norepinephrine receptor stimulation inhibits the activtity in the 5-HT neurons: clonidine reduces primarily the relase of 5-HT without an immediate effect on its synthesis. The differences observed among the various cerebral areas might be explained by the fact that relations between nor-epinephrine and 5-HT neurons do not exist identically in all cerebral structures.