Glial fibrillary acidic immunoreactivity in brain was examined in normal animals and in rats subjected to chronic hypoxia. Animals were exposed to a chronic normobaric adaptive hypoxia with decreasing amounts of oxygen (finally 6%) for a period of 59 and 114 days, respectively. In paraffin-embedded sections the glial fibrillary acidic protein immunoreactivity in normal and hypoxic animals was examined at three coronal levels. A mild glial fibrillary acidic protein immunoreactivity in the perivascular glial layer, external glial limitans membrane and periventricular astrocytes, as well as in some areas of hippocampus and cerebellum, was noted in normal animals. Chronic hypoxia for 114 days resulted in a marked increase of glial fibrillary acidic protein immunoreactivity in dentate gyrus of hippocampus, Bergmann glia of the cerebellum, internal capsule and pyramidal tract. On the other hand, the glial fibrillary acidic protein activity following 59 days hypoxic exposure was almost the same as controls. These results show that systemic deep chronic hypoxia (depending on the intensity and the duration) activates the endogenous expression of glial fibrillary acidic protein in astrocytes of specific brain regions. The probable significance of this finding is discussed.