Previous results have indicated that application of serotonin (5-HT) onto noradrenergic locus coeruleus (LC) neurons selectively attenuates the response of these cells to excitatory amino acids (EAAs). Other studies revealed that certain sensory responses of LC neurons are mediated by EAA inputs. We examined the role of endogenous 5-HT in modulating sensory responses of LC neurons that are EAA-mediated. LC neurons recorded in rats pretreated with the serotonin (5-HT) depletor, p-chlorophenylalanine (PCPA), exhibited increased responsiveness to electrical stimulation of a rear footpad. Conversely, injection of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), reversed this effect of PCPA and attenuated this sensory response of LC neurons in drug-naive animals. Neither treatment altered the spontaneous discharge rate of LC neurons. These results are consistent with previous findings indicating that 5-HT has potent but selective effects on EAA-mediated responses of LC neurons, and in addition point to a possible functional role for endogenous 5-HT in controlling sensory-evoked LC activity.