The adult rat adapts to prolonged moderate hypobaric hypoxia by polycythemia, increased brain vascularity, and increased density of the brain capillary glucose transporter (GLUT-1). We now report on the time-course and reversibility of these adaptive alterations. Adult male Wistar rats were subjected to hypobaric hypoxia at 0.5 atmosphere for periods of 4 days or 1, 2 or 3 weeks, and compared to normoxic littermate controls. Reversibility of the effects of hypoxia was studied in rats subjected to hypobaric hypoxia for 3 weeks and then allowed to recover at normobaric conditions for 3 additional weeks. Cerebral vascularity was studied in cross-sections of the cerebral cortex that were immunocytochemically stained with a GLUT-1 antibody. The density of GLUT-1 was determined in isolated cerebral microvessels by quantitative autoradiography of immunoblots. Blood hematocrit and cerebral microvascularity did not significantly increase after 4 days of hypoxia, but were significantly increased at 1, 2 and 3 weeks of hypoxia. Three weeks of normoxic recovery after 3 weeks of hypoxia reversed the polycythemia and cerebral hypervascularity. However, the density of GLUT-1 in isolated cerebral microvessels, which was significantly increased after 1 and 3 weeks of hypoxia, remained elevated after 3 weeks of normoxia.