To determine whether the stimulatory effect of CO 2 on the peripheral chemoreceptors is due to molecular CO 2, H + or both we measured steady-state ventilation (V̇E) during normoxia in 9 and during hypoxian in 5 chloralose-urethane anaesthetized cats using the artificial brain stem perfussion technique. This technique allows one to manipulate independently the Pa CO 2 , Pa O 2 and the pHa of the blood in the systemic circulation (peripheral) and the blood perfusing the brain stem (central). Keeping the central conditions constant the H + and CO 2 concentrations in the systematic circulation were changed by i.v. infusion of 0.3 M HCl or 0.6M NaHCO 3 and by giving the animal different CO 2 mixtures to inhale. The peripheral H + concentration ([H +]p) range covered was from 27 to 103 nmol·1 −1, the peripheral arterial CO 2 tension (Pa p CO 2 ) range from 2.3 kPa to 8.4 kPa. Fitting the data the function V ̇ E = a[ H +] p + bPa p CO 2 + c revealed that the coefficient b was not significantly different from zero at the 0.05 level during normoxia and hypoxia. The mean value (±SEM) found for the coefficient a was 33.0 ± 3.6 at normoxia and 36.0 ± 14.5 ml · min −1 · nM −1 at hypoxia. We conclude that the steady-state ventilatory response due to the simulation of the peripheral chemoreceptors with CO 2 is mediated by H +. The effects of molecular CO 2 are negligible.