We simultaneously performed near infrared spectroscopy (NIRS) and transcranial Doppler (TCD) to evaluate the effects of hypercapnia as well as of scalp ischemia on the blood flow at two different depth levels within the brain and of the scalp vessels. A decrease in the backscattered light intensity, meaning an increment of blood volume, was detected at the end of hypercapnia in all healthy subjects. This decrement was partly masked by ischemia in the cutaneous vessels. In 2 patients with a monohemispheric lesion in the middle cerebral artery (MCA) territory, an increase in NIRS response was found in the healthy hemisphere, while in the stroke side the CO2-induced changes were negligible. TCD data showed a similar increment of blood flow velocity to the hypercapnia in both hemispheres, with no differences between the affected and normal side in 1 patient, whereas in the second one, no increment was observed on the affected side, probably due to internal carotid artery stenosis. The two methods nicely integrate: TCD mainly tests subcortical changes in the MCA flow, while NIRS is exquisitely sensitive to cortical arterioles and capillary blood flow modifications.