Exposure to chronic hypoxia (CH) leads to ventilatory acclimatisation to hypoxia (VAH) which manifests as an increase in both resting ventilation and the sensitivity of the respiratory system to acute hypoxia. This study investigated whether changes in GABA-mediated neurotransmission in the nucleus of the solitary tract (NTS) contributes to VAH. Control and CH rats (9 days of hypobaric hypoxia; 0.5 atm) were subjected to acute hypoxic breathing trials (poikilocapnic and isocapnic) using whole body plethysmography, before and after bilateral microinjections of the GABA-receptor antagonists bicuculline (GABAA antagonist) and CGP-35348 (GABAB antagonist) into the caudal NTS. Bicuculline only affected breathing in CH rats, significantly reducing resting ventilation and breathing frequency during the acute hypoxic ventilatory response. Bicuculline plus CGP-35348 produced similar effects to bicuculline alone. The results indicate that changes in GABAA but not GABAB receptor-mediated neurotransmission within the NTS are involved in central changes to respiratory control that accompany VAH.