I used basic physiological principles to develop a simple feed-forward method of attaining and controlling target arterial PO2 and PCO 2 through the manipulation of alveolar gas concentrations in spontaneously breathing subjects. Contrary to common wisdom which, as stated in the Journal of Applied Physiology, states that "...the CO2 and O2 effects on the CBF are physiologically inseparable", my method is able to vary the partial pressure of each gas independently. I was therefore able to examine the effects of each gas separately on CBF. Using a transcranial Doppler to monitor cerebral blood flow I showed that cerebrovascular response to changes in alveolar PCO2 at sustained normoxia has a very short time constant which implies that it responds directly to arterial rather than brain tissue PCO2. Second, I showed that changes in arterial PO 2 confounds interpretation of common CO2-induced cerebrovascular reactivity measures when BOLD MRI signal is used to indicate cerebral blood flow.