Abstract We have previously observed that the guinea-pig appears to have a relatively poor ventilatory (V̇ E) response to hypoxia, compared to other mammals. Therefore, in this study, we questioned the ability of the carotid bodies (primary peripheral chemoreceptors) in the guinea-pig to detect hypoxia. The ventilatory responses to poikilocapnic hypoxia (8% O 2), poikilooxic hypercapnia (8% CO 2), hyperoxia (100% O 2) and cyanide (NaCN — 200 μg/kg, i.v.) were assessed before and after carotid body denervation (CBD) in anaesthetized guinea-pigs. Although CBD attenuated the V̇ E responses to hypercapnia and cyanide, it had no effect on normoxic breathing or the V̇ E responses to hypoxia or hyperoxia. In a separate group of guinea-pigs, nerve activity was recorded from single or few-fibre preparations of the carotid sinus nerve (CSN). Basal chemoreceptor activity could not be detected from any of the nerve preparations. NaCN and hypercapnia consistently provoked an increase in neural activity. In contrast, hypoxia never clearly increased activity in any of the single or few-fibre preparations isolated from the CSN. In conclusion, although the carotid bodies of the guinea-pig, like those of other mammals, are able to detect hypercapnia and histotoxic hypoxia and elicit a reflex increase in V̇ E, they are essentially hypoxia-insensitive. The latter may explain, at least in part, the relatively poor V̇ E response to hypoxia shown by the guinea-pig.