Intravenous bolus injection of KCN (40 microg) elicited brief but pronounced tachypnea, bradycardia and pressor response, and led to a 37% increase in 5-hydroxytryptamine (serotonin) (5-HT) release in the locus coeruleus (LC) of freely moving rats. Slow infusion of KCN (15 microg/min) for 10 min induced only a slight pressor response, but increased the respiration rate (+39 breaths/min), as well as 5-HT release in the LC (+60%) throughout the infusion. In rats with transected chemoreceptor afferents, neither injection or infusion of KCN changed 5-HT release, suggesting that in intact animals, the effect on extracellular 5-HT was due to activation of peripheral chemoreceptors. In summary, we report that peripheral chemoreceptor activation enhances 5-HT release in the LC, indicating that 5-HT might be involved in the modulation of LC activity by ascending chemosensory information.