Breath-by-breath variability of the end-tidal partial pressure of CO2 (Pet(CO2)) has been shown to be associated with cerebral blood flow (CBF) fluctuations. These fluctuations can impact neuroimaging techniques that depend on cerebrovascular blood flow. We hypothesized that controlling Pet(CO2) would reduce CBF variability. Dynamic end-tidal forcing was used to control Pet(CO2) at 1.5 mm Hg above the resting level and to hold the end-tidal partial pressure of oxygen (Pet(O2)) at the resting level. Peak blood velocity in the middle cerebral artery (MCA) was measured by transcranial Doppler ultrasound (TCD) as an index of CBF. Blood velocity parameters and timing features were determined on each waveform and the variance of these parameters was compared between Normal (air breathing) and Forcing (end-tidal gas control) sessions. The variability of all velocity parameters was significantly reduced in the Forcing session. In particular, the variability of the average velocity over the cardiac cycle was decreased by 18.2% (P < 0.001). For the most part, the variability of the timing parameters was unchanged. Thus, we conclude that controlling Pet(CO2) is effective in reducing CBF variability, which would have important implications for physiologic neuroimaging.