In order to know the pathophysiological mechanisms underlying radiation brain injury, cerebral blood flow and blood-brain barrier integrity were studied using N-isopropyl-p-[123l]iodoamphetamine (IMP) and [14C]-alpha-aminoisobutyric acid (AIB), respectively, in the rat focal proton radiation model (a single dose of 30 or 60 Gy radiation with 70 MeV proton beams). One, 2, 4, and 5.5 months after irradiation, [123l]IMP and [14C]AIB were intravenously injected and uptake of IMP and AIB in the cerebral cortex, striatum, hippocampus, and thalamus was measured. Significant decreases in IMP uptake were observed in the cerebral cortex and thalamus of the irradiated side at 4 and 5.5 months after 60 Gy irradiation; the effects at 5.5 months were more prominent than those at 4 months. AIB uptake markedly increased in all the brain regions of the irradiated side at 5.5 months after 60 Gy irradiation, and at 4 months, only in the hippocampus. The results suggest that there are dose- and time-dependent responses in radiation effects and regional differences in tissue vulnerability to radiation. Proton focal radiation model appears to be a useful model for studies of radiation brain injury in small animals such as rats.