To determine the type of serotonergic receptor involved in the modulation of noradrenergic neuronal activity in the locus coeruleus, the effects of 4 systemically administered serotonergic drugs were tested on the firing rate of noradrenergic neurons in the locus coeruleus of rats under chloral hydrate anaesthesia. The serotonergic agonist, quipazine (1 mg/kg), and the selective 5-HT2 agonist, DOB (50-100 micrograms/kg), induced a pronounced decrease of the discharge frequency. This effect could be prevented or reversed by the selective 5-HT2 antagonist, ketanserin (4-8 mg/kg). Ketanserin alone and the 5-HT1 agonist, RU 24969, had no or a weak excitatory action on the neuronal activity of the locus coeruleus. We conclude that the serotonergic control of noradrenergic neurons in the locus coeruleus is mediated by post-synaptic 5-HT2 receptors because the quipazine-ketanserin effects on this unit activity persisted after depletion of serotonergic presynaptic stores.