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Visual stimulation was combined with controlled hyperventilation and carbon dioxide inhalation to perform fMRI at six levels of end\u2010expiratory pCO<jats:sub>2<\/jats:sub> (P<jats:sc>ETCO<\/jats:sc><jats:sub>2<\/jats:sub>) between 20 and 70 mm Hg. <jats:italic>T<\/jats:italic><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-stack-2.gif\" xlink:title=\"urn:x-wiley:07403194:media:MRM1187:tex2gif-stack-2\" \/> in visual cortex during baseline conditions (light off) increased nonlinearly from 20 to 70 mm Hg, from 61.1 \u00b1 4.2 ms to 72.0 \u00b1 4.6 ms. Changes in <jats:italic>T<\/jats:italic><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-stack-3.gif\" xlink:title=\"urn:x-wiley:07403194:media:MRM1187:tex2gif-stack-3\" \/> due to visual stimulation increased 2.1\u2010fold, from 1.2 \u00b1 0.6 ms at 20 mm Hg to 2.5 \u00b1 0.7 ms at 50 mm Hg. An almost complete loss of functional contrast was measured at 70 mm Hg. The model of MR signal dephasing by Yablonskiy and Haacke (Mag Reson Med 1994;32:749\u2013763) was used to predict changes in cerebral blood flow (CBF), which were found to be consistent with results from previous positron emission tomography (PET) studies. This study further emphasizes that global CBF changes (due to P<jats:sc>ETCO<\/jats:sc><jats:sub>2<\/jats:sub> changes even in the physiological range) strongly influence fMRI contrast and need to be controlled for. 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