Near-infrared spectroscopy (NIRS) enables continuous non-invasive quantification of blood and tissue oxygenation, and may be useful for quantification of cerebral blood volume (CBV) changes. In this study, changes in cerebral oxy- and deoxyhemoglobin were compared to corresponding changes in CBF and CBV as measured by positron emission tomography (PET). Furthermore, the results were compared using a physiological model of cerebral oxygenation. In five healthy volunteers changes in CBF were induced in a randomized order by hyperventilation or inhalation of 6% CO(2). Arterial content of O(2) and CO(2) was measured several times during each scanning. Changes in deoxyhemoglobin (deltaHb), oxyhemoglobin (deltaHbO(2)) and total hemoglobin (deltaHb(tot)) were continuously recorded with NIRS equipment. CBF and CBV was also determined in MRI-coregistered PET-slices in regions determined by the placement of the two optodes, as localized from the transmission scan. The PET-measurements showed an average CBV of 5.5+/-0.74 ml 100 g(-1) in normoventilation, with an increase of 29% during hypercapnia, whereas no significant changes were seen during hyperventilation. CBF was 51+/-10 in normoventilation, increased by 37% during 6% CO(2) and decreased by 25% during hyperventilation. NIRS showed significant increases in oxygenation during hypercapnia, and a trend towards decreases during hyperventilation. Changes in CBV measured with both techniques were significantly correlated to CO(2) levels. However, deltaCBV(NIRS) was much smaller than deltaCBV(PET), and measured NIRS parameters smaller than those predicted from the model. It is concluded that while qualitatively correct, NIRS measurements of CBV should be used with caution when quantitative results are needed.