Hypoxia-induced dopamine (DA) release from carotid body (CB) glomus cells and activation of post-synaptic D2 receptors has been proposed to play an important role in the neurotransmission process between the glomus cells and afferent nerve endings. In order to better resolve the role of D2 receptors, we examined afferent nerve activity, catecholamine content and release and ventilation of genetically engineered mice lacking D2 receptors (D2^-/-). Single-unit afferent nerve activities of D2^-/-, in vitro, were significantly reduced by 45 and 25% compared to wild type (WT) during superfusion with saline equilibrated with mild hypoxia (PO₂ ~ 50torr) or severe hypoxia (PO₂ ~ 20 torr), respectively. Catecholamine release in D2^-/- mice was enhanced by 125% in mild hypoxia and 75% in severe hypoxia compared to WT mice and the rate of rise was increased in D2^-/- mice. We conclude that carotid body transduction of hypoxia is still present in D2^-/- mice, but the response magnitude is reduced. However, the ventilatory response to acute hypoxia is maintained, perhaps due to an enhanced processing of chemoreceptor input by brainstem respiratory nuclei.