Because meningiomas tend to recur after (partial) surgical resection, radiotherapy is increasingly being applied for the treatment of these tumors. Radiation dose levels are limited, however, to avoid radiation damage to the surrounding normal tissue. The radiosensitivity of tumors can be improved by increasing tumor oxygen levels. The aim of this study was to investigate if breathing a hyperoxic hypercapnic gas mixture could improve the oxygenation of meningiomas. Blood oxygen level-dependent magnetic resonance imaging and dynamic Gadolinium (Gd)-DTPA contrast-enhanced MRI were used to assess changes in tumor blood oxygenation and vascularity, respectively. Ten meningioma patients were each studied twice; without and with breathing a gas mixture consisting of 2% CO(2) and 98% O(2). Values of T(2)* and the Gd-DTPA uptake rate k(ep) were calculated under both conditions. In six tumors a significant increase in the value of T(2)* in the tumor was found, suggesting an improved tumor blood oxygenation, which exceeded the effect in normal brain tissue. Contrarily, two tumors showed a significant T(2)* decrease. The change in T(2)* was found to correlate with both k(ep) and with the change in k(ep). The presence of both vascular effects and oxygenation effects and the heterogeneous response to hypercapnic hyperoxia necessitates individual assessment of the effects of breathing a hyperoxic hypercapnic gas mixture on meningiomas. Thus, the current MRI protocol may assist in radiation treatment selection for patients with meningiomas.