Activation of the laryngeal mucosa results in apnea that is mediated through, and can be elicited via electrical stimulation of, the superior laryngeal nerve (SLN). This potent inhibitory reflex has been suggested to play a role in the pathogenesis of apnea of prematurity and SIDS and is attenuated by theophylline and blockade of GABA_A receptors. However, the interaction between GABA and adenosine in the production of SLN stimulation induced apnea has not been previously examined. We hypothesized that activation of adenosine A_2A receptors will enhance apnea induced by SLN stimulation while subsequent blockade of GABA_A receptors will reverse the effect of A_2A receptor activation. The phrenic nerve responses to increasing levels of SLN stimulation were measured before and after sequential intracisternal administration of adenosine A_2A receptor agonist CGS (n=10) and GABA_A receptor blocker bicuculline (n=7) in ventilated, vagotomized, decerebrate and paralyzed newborn piglets. Increasing levels of SLN stimulation caused progressive inhibition of phrenic activity and lead to apnea during higher levels of stimulation. CGS caused inhibition of baseline phrenic activity, hypotension and enhancement of apnea induced by SLN stimulation. Subsequent bicuculline administration reversed the effects of CGS and prevented the production of apnea when compared to control at higher SLN stimulation levels. We conclude that activation of adenosine A_2A receptors enhances SLN stimulation induced apnea probably via a GABAergic pathway. We speculate that SLN stimulation causes endogenous release of adenosine that activates A_2A receptors on GABAergic neurons resulting in the release of GABA at inspiratory neurons and subsequent respiratory inhibition.