In decerebrate, paralyzed, vagotomized and artificially ventilated cats, serotonin (5-HT) and its analogues, microinjected into the hypoglossal (XII) motor nucleus, altered the activity of the genioglossal branch of XII nerve. 5-HT, carboxamidotryptamine malcate (5-CT) and DOI (1–5 mM) increased the activity by over 200%. Methysergide reversed this increase. Methysergide, mianserin, or ketanserin (100–250 nl, 1 mM) reduced the spontaneous hypoglossal activity by 20–50%. Buspirone, 8-OH-DPAT and (−)-propranolol were without effect. Thus, 5-HT provides a substantial tonic excitatory drive to XII motoneurons. The 5-HT receptors involved are likely to be type 1C or 2, but uncertainty regarding the affinity profiles of the drugs used in in vivo conditions in the cat precludes a definite identification.