Hypoxia causes changes in the rate of synthesis or release of neurotransmitters in the brain. The accumulation of serotonin (5-HT) in the central nervous system might cause hypoxic respiratory depression. In the present study, we aimed to examine the role of central 5-HT on normoxic and acute hypoxic ventilatory depression (AHVD) in peripheral chemoreceptors denervated rabbits. All experiments were performed in peripherally chemodenervated rabbits anesthetized with intravenous injection of urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). For intracerebroventricular (ICV) administration of 5-HT (20 mu g/kg) and ketanserin (10 mu g/kg), a cannula was placed in left lateral ventricle by stereotaxic method. Respiratory frequency (f(R)), tidal volume (V-T), ventilation minute volume (V-E) and systemic arterial bood pressure (BP) were recorded in each experimental phases and mean arterial pressure was calculated (MAP). Heart rate (H-R) was also determined from the pulsation of BP. The effects of ICV serotonin and ICV ketanserin on the indicated parameters during air breathing (normoxia) and breathing of hypoxia (8% O-2 - 92% N-2) were investigated. During hypoxia, fit, V-T, V-E, MAP and H-R decreased, and AHVD was thus obtained. ICV injection of 5-HT during normoxia caused significant increases in V-T (P < 0.001) and in V-E (P < 0.01). On the other hand, ICV 5-HT injection reduced the degree of AHVD in peripherally chemodenervated rabbits during hypoxia (f(R); P < 0.05, V-T; P < 0.05 and V-E; P < 0.01). After ICV injection of ketanserin, the enhancement of 5-HT on V-E was prevented during normoxia. On the breathing of hypoxic gas after ICV ketanserin, the degree of AHVD was augmented. In conclusion, our findings suggested that central 5-HT increases normoxic ventilation and reduces the degree of AHVD during hypoxia and that ICV ketanserin prevents the stimulatory effect of 5-HT on respiration and augments AHVD.