OBJECTIVE: To observe the effect of hypoxia on the activity of the tissue-type plasminogen activator (TPA) of brain microvascular endothelial cells in mice. METHODS: Microvascular endothelial cells obtained from the brains of newborn mice were cultured in primary and passage under room air and hypoxic conditions to observe the variation in TPA activities. TPA activity was assayed using the enzyme linked immunosorbent assay (ELISA) technique. RESULTS: Following hypoxia, TPA activity in endothelial cells increased in primary culture compared with the controls: (22.5±1.5)×10-2 IU/ml vs (19.4±1.7)×10-2 IU/ml (P<0.01). TPA activity following hypoxia was not altered in passaged cells. CONCLUSIONS: Neuronal damage following hypoxia may be associated with increased endothelial TPA activity.