PREVIOUS findings in animals demonstrated that the noradrenergic coeruleospinal system exerts a tonic facilitation on spinal reflexes and that activation of α2-autoinhibitory receptors can be responsible for a disfacilitation of the spinal activity. To investigate this issue further, we examined whether this system is also involved in descending facilitatory control of spinal motoneurons in healthy humans. The H-reflex technique was utilized to assay the motoneuronal excitability. The ratio between the maximal reflex response (H) and maximal direct response (M) was determined in each subject and was calculated at 10 min intervals before and after i.v. administration of the α2-agonist clonidine (0.5 μg/kg). In all subjects a marked decrease of the H/M ratio, due to depression of the H response, occurred 10 min following the clonidine injection and reached its maximum within 30 min. No significant changes of blood pressure values were provoked by drug injections. These results suggest that an autoinhibitory action may be induced by α2-receptor activation of locus coeruleus neurons in humans, and that this device may serve as a mechanism for a myotonolytic action on spinal motoneurons.