Introduction The respiratory control of the upper airway muscles, mainly of the genioglossus (GG), is involved in the collapsus of the oropharynx, the main event in the physiopathology of the Obs-tructive Sleep Apnea Syndrome (OSAS). One major objective is the understanding of the neuromodulation of the hypoglosssus (XII) nudeus (which innervâtes the GG) as well as the synchronized acti-vity with that of the diaphragm (DIA) via brainstem pathways involved in the regulation of breathing and sleep. The first objective was to study whether central injections of 5-HT1A (8-OHDPAT), 5HT2A/2C agonist (DOI) and 5-HT1B antagonist (SB224289) both modulate the DIA and GG respiratory activities in anaesthe-tised rat. The second objective was to evaluate the time and dose-related effects with the same drugs. Method The electromyogram (EMG) of the GG and DIA were recorded in 20 anaesthetized rats. The respiratory rate (RR), the respiratory activities of the DIA and GG (amplitude, surface, inspira-tory duration) were analysed after intra-cerebroventricular injections of 8-OHDPAT, DOI and SB224289 and compared to NaCl injections. Results The RR was lightly decreased with the 8-OHDPAT and the DOI. The 8-OHDPAT and the SB224289 significantly increase the amplitude and surface of the GG respiratory activity without effects on the GG inspiratory duration and the DIA. The DOI significantly increase both the DIA and GG respiratory activities (amplitude, surface and inspiratory duration). A dose-related effect was observed on both the amplitude of the GG tonic and phasic activities respectively with the DOI and the 8-OHDPAT. However, this dose-related effect of the GG phasic activity (8-OHDPAT) and tonic activity (DOI) is much more pro-nounced on the amplitude of the response than the duration of the response. Conclusions The 5-HT1A could modulate the GG respiratory activity via the inhibiting autoreceptors from the direct (medullary raphe) and indirect (dorsal raphe) afferents to the XII nucleus ( Respir Res 2001 ; 2 : 286-94). The SB224289 could inhibit pre-synaptically the 5-HT1B receptors located on the glutamatergic and cholinergic afferents to the XII nucleus. The 5-HT2A/2C could be involved in the central modulation of the respiratory pat-tern via the dorsal respiratory group. To stimulate the muscular tone of the upper airway (GG) throughout the sleep period, we sug-gest serotonergic drugs might be continuously delivered via a pump in order to sustain a constant serotonergic rate within the brain.