Changes in the nitric oxide system of the hippocampus from rats submitted to hypobaric hypoxia were investigated. Adult rats were exposed to a simulated altitude of 8,325 m (27,000 ft) for 7 h and killed after 0 h, 1, 3, 5, 10 and 20 days of reoxygenation. The number of neuronal nitric oxide synthase immunoreactive neurons and their dendritic plexus, as well as neuronal nitric oxide synthase immunoblotting densitometry and calcium-dependent activity increased from 0 h to 3 days of reoxygenation. In addition, endothelial nitric oxide synthase immunoreactivity peaked after 7 h of hypobaric hypoxia. Nitrotyrosine immunoreactivity showed an increase in the pyramidal cells of CA2-CA3 and in glial cells surrounding the blood vessels after 0 h, 1 and 3 days of reoxygenation. Immunoblotting densitometry of 1 of the 2 nitrotyrosine-immunoreactive bands detected also increased after 0 h and 1 day of reoxygenation. Inducible nitric oxide synthase immunoreactivity was found only in some blood vessels after 0 h, 1 and 3 days of reoxygenation, but no changes in inducible nitric oxide synthase activity or immunoblotting were detected. We conclude that transient activation of the nitric oxide system constitutes a hippocampal response to hypobaric hypoxia.