The brains of young adult rats were irradiated with doses of 500-4000 rad. At intervals of 3-15 months after irradiation regional changes in the functional vasculature were investigated using the iodoantipyrine extraction technique. Modifications in vascular function were restricted to animals locally irradiated with doses of 2000 and 3000 rad. The first change was observed three months after irradiation and was characterized by a reduction in antipyrine extraction in the mid-brain and brain stem of animals irradiated with 2000 rad. At six and nine months after exposure to both 2000 and 3000 rad significant increases in antipyrine extraction were found in the four brain regions examined, although the effect was greatest in the mid-brain. These results are compared and contrasted with functional changes reported in other normal tissues; the link between these functional changes in the brain vasculature and the appearance of gross vascular lesions after a latent period of one year is discussed. It is suggested that the increase in iodoantipyrine extraction represents a regulatory reaction by the vasculature of the brain to tissue hypoxia and that focal vascular lesions in the brain occur as a consequence of the failure of this reaction to hypoxia.