The retrotrapezoid nucleus (RTN), located close to the ventral medullary surface, contains central chemoreceptors that are activated by hypercapnia. In anesthetized animals, pharmacological inhibition of RTN causes apnoea, abolishes the response to increased CO₂ and blocks the peripheral chemoreflex (1). The physiological role of the RTN in non anesthetized animals is less clear. We have performed bilateral microinjections of GABA_A receptor agonists (muscimol or isoguvacine) in the RTN of decerebrate artificially-perfused in situ rat preparations (2). Rats were decerebrated under deep halothane anaesthesia as assessed by an absence of reflex limb withdrawal to noxious pinching (as per ref. 2). Once decerebrate (i.e. insentient), halothane administration was discontinued making these preparations devoid of the undesirable effects of anaesthesia. The ventral medullary surface was surgically exposed and agonists were microinjected in the RTN under visual control while the phrenic nerve activity (PNA) was recorded simultaneously. Muscimol injections (1.75 mM, 30-60 nl, n=7) to the RTN caused apnoea and prevented any response to hypercapnia (8% CO₂). Peripheral chemoreceptor stimulation (0.03% NaCN) briefly restored bursts of PNA (2-5 cycles). Recovery from the muscimol effect occurred within 1-3 h. Conversely, isoguvacine injections (10 mM, 30-60 nl, n=9) into identical regions as confirmed histologically did not affect spontaneous PNA or peripheral chemoreception but induced a significant 85% decrease in the PNA response to 8% CO₂ (P<0.05, t test). Thus, in this in situ rat preparation with ventral medullary surface exposed, ventilatory responses to central and peripheral chemoreceptor stimulation can be differentially altered depending on the GABA_A receptor agonist employed to inhibit the RTN.