We have utilized an anaesthetized rat model of insulin-induced hypoglycaemia to test the hypothesis that peripheral chemoreceptor gain is augmented during hypermetabolism. Insulin infusion at 0.4 U kg-1 min-1 decreased blood glucose concentration significantly to 3.37 ± 0.12 mmoll-1. Whole-body metabolism and basal ventilation were elevated without increase in Pa,CO2 (altered non-significantly from the control level, to 37.3 ± 2.6 mmHg). Chemoreceptor gain, measured either as spontaneous ventilatory airflow sensitivity to Pa,CO2 during rebreathing, or by phrenic minute activity responses to altered Pa,CO2 induced by varying the level of artificial ventilation, was doubled during the period of hypermetabolism. This stimulatory effect was primarily upon the mean inspiratory flow rate, or phrenic ramp component of breathing and was reduced by 75% following bilateral carotid sinus nerve section. In vitro recordings of single carotid body chemoafferents showed that reducing superfusate glucose concentration from 10 mM to 2 mM reduced CO2 chemosensitivity significantly from 0.007 ± 0.002 Hz mmHg-1 to 0.001 ± 0.002 Hz mmHg-1. Taken together, these data suggest that the hyperpnoea observed during hypermetabolism might be mediated by an increase in the CO2 sensitivity of the carotid body, and this effect is not due to the insulin-induced fall in blood glucose concentration.