The role of peripheral and central dopaminergic mechanisms in respiratory control was studied in anesthetized cats. In one series, we simultaneously measured carotid chemoreceptor and ventilatory responses to hypoxia and hypercapnia before and after a saturation dose of intravenous domperidone, a peripheral dopamine (D2) receptor antagonist. Both carotid chemoreceptor and ventilatory responses were augmented by domperidone essentially in proportion, suggesting that they reflected the increase of peripheral chemoreceptor activity. Haloperidol which crosses into the brain from blood, given subsequent to domperidone, did not further affect carotid chemoreceptor responses but attenuated ventilatory responses to hypoxia without significantly altering those to hypercapnia. Thus, the additional ventilatory effect of haloperidol is mediated through central dopaminergic mechanisms involving peripheral chemoreflex pathway alone. In another series, the anesthetized cats were paralyzed and artificially ventilated to study carotid chemoreceptor responses to step increases in the end-tidal PCO2 before and after domperidone. Domperidone significantly augmented the responses to CO2. The results support the hypothesis that both peripheral and central dopaminergic mechanisms play a significant modulatory role in chemoreflex respiratory control.