The most physiologically important sensors for systemic glucoregulation are located in extra-cranial sites. Recent evidence suggests that the carotid body may be one such site. We assessed rat carotid body, afferent neural output in response to lowered glucose, indirectly, by measurement of ventilation and directly, by recording single or few-fibre chemoafferent discharge, in vitro. Insulin (0.4 U Kg^-1 min^-1)-induced hypoglycaemia (blood glucose reduced by ca. 50% to 3.4±0.1 mmol L^-1) significantly increased spontaneous ventilation (V_E) in sham-operated animals but not in bilateral carotid sinus nerve sectioned (CSNX) animals. In both groups, metabolic rate (measured as V_O2) was almost doubled during hypoglycaemia. The ventilatory equivalent (V_E/V_O2) was unchanged in the sham group leading to a maintained control level of P_a,CO2, but V_E/V_O2 was significantly reduced in the CSNX group, giving rise to an elevation of 6.0±1.3 mmHg in P_a,CO2. When pulmonary ventilation in sham animals was controlled and maintained, phrenic neural activity increased during hypoglycaemia and was associated with a significant increase in P_a,CO2 of 5.1±0.5 mmHg. Baseline chemoreceptor discharge frequency, recorded in vitro, was not affected, and did not increase when the superfusate [glucose] was lowered from 10 mM to 2 mM by substitution with sucrose; 0.40±0.20 Hz to 0.27±0.15 Hz respectively (P>0.20). We suggest, therefore, that any potential role of the carotid bodies in glucose homeostasis in vivo is mediated through its transduction of some other metabolically derived blood-borne factor rather than glucose per se and that this may also provide the link between exercise, metabolic rate and ventilation.