Arterial blood gas levels are maintained through respiratory chemoreflexes, mediated by central chemoreceptors in the CNS and peripheral chemoreceptors located in the carotid bodies. The interaction between central and peripheral chemoreceptors is controversial, and few studies have investigated this interaction in awake, healthy humans, owing, in part, to methodological challenges. We investigated the interaction between the central and peripheral chemoreceptors in healthy humans using a transient hypoxia test (three consecutive breaths of 100% N 2 ; TT-HVR), which targets the temporal domain and stimulus specificity of the peripheral chemoreceptors. The TT-HVRs were superimposed upon three randomized background levels of steady-state inspired fraction of normoxic CO 2 (F I,CO 2 ; 0, 0.02 and 0.04). Chemostimuli [calculated oxygen saturation (S cO 2 )] and respiratory variable responses [respiratory rate (R R ), inspired tidal volume (V TI ) and ventilation ( VI )] were averaged from all three TT-HVR trials at each F I,CO 2 level. Responses were assessed as: (1) a change (∆) from baseline; and (2) indexed against ΔS cO 2 . Aside from a significantly lower ∆V TI response in 0.04 F I,CO 2 (P = 0.01), the hypoxic rate responses (∆R R or ∆R R /ΔS cO 2 ; P = 0.46 and P = 0.81), hypoxic tidal volume response (ΔV TI ∕ΔS cO 2 ; P = 0.08) and the hypoxic ventilatory responses (Δ VI and Δ VI ∕ΔS cO 2 ; P = 0.09 and P = 0.31) were not significantly different across F I,CO 2 trials. Our data suggest simple addition between central and peripheral chemoreceptors in VI , which is mediated through simple addition in R R responses, but hypo-addition in V TI responses. Our study adds important new data in reconciling chemoreceptor interaction in awake, healthy humans and is consistent with previous reports of simple addition in intact rodents and humans.