Humans who are born and raised at high altitude possess a blunted breathing response to hypoxia. The guinea-pig also has a blunted breathing response to hypoxia [1], which may be linked to its high altitude origin in South America. Our laboratory has shown that the carotid bodies of the guinea-pig are not required for the breathing response to hypoxia [1]. Whether the carotid bodies can actually detect hypoxia is uncertain because the central depressive effects associated with hypoxia may attenuate the breathing response to an otherwise potent carotid body stimulant. In a recent study, we looked for evidence of chemoreceptor activity in the whole carotid sinus nerve (CSN), but found that the whole CSN activity was dominated by baroreceptor afferent activity [2]. In this study activity was recorded from single or few-fibre CSN filaments during application of the chemoreceptor stimulants NaCN (200 μgkg-1 i.v.), 8% CO2 (60 s) and 8% O2 (60 s), from guinea-pigs (n = 10; ~420 g; ~50 days old) that were anaesthetised with ketamine/xylazine (20/1 mgkg-1). Of the 10 guinea-pigs, only 8 fibre preparations containing chemoreceptor activity were successfully obtained from 4 guinea-pigs. In general, most of the isolated nerve filaments were multi-fibre preparations. Basal chemoreceptor activity could not be detected. However, NaCN and hypercapnia increased activity in 5 of the fibre preparations that were otherwise silent, or that contained 1 or 2 baroreceptor fibres. The magnitude of response varied considerably between filaments because of the different number of individual fibres in each preparation and, thus, the difference in the actual count of action potentials. Only one of the fibre preparations responded to hypoxia with an increase in activity; no fibres responded with a decrease in activity. The physiological relevance of the latter results could be similar to that of the aortic depressor nerve (ADN) in the rat. Brophy et al. revealed that, in contrast to the general consensus, the rat ADN does contain chemoreceptor afferent fibres, and that such fibres are stimulated by chemoreceptor stimulants [3]. Kobayashi et al. agreed that chemoreceptor fibres were present, but concluded that the rat ADN does not contain a functionally significant number of chemoreceptor afferent fibres that could appreciably contribute to the generation of chemoreflexes [4]. The present study has shown that the carotid bodies of the guinea-pig can detect NaCN and hypercapnia, as expected, and also hypoxia, although the latter was a comparatively weak stimulant. In conclusion, the physiological relevance of the carotid body of the guinea-pig for the ventilatory responses to hypoxia remains uncertain.