Modulation of the function of the blood-brain barrier (BBB) in the hypothalamus was investigated after the intoxication with 3-nitropropionic acid (3-NPA) that inhibits the succinate dehydrogenase. 3-NPA was administered to rats for three days. Following transcardial perfusion, brain sections were studied by immunohistochemistry. On the 2nd or 3rd day after 3-NPA, strong immunoreactions for blood-borne macromolecules, IgG, appeared in the striatum and hippocampus. Glial fibrillary acidic protein (GFAP) positive astroglias distributed heterogeneously, and induced nitric oxide synthase (iNOS) positive cells appeared around the vessels. A week later, bilateral lesions were detected in these areas. In the hypothalamus, there appeared a moderate immunoreaction for IgG, but no expression of iNOS. GFAP positive astroglias were rich especially around the vessels, and no loss in microtubule-associated protein 2 (MAP2) immunoreaction was detected, suggesting an intact BBB structure and no neuronal loss following 3-NPA intoxication. Data indicate that hypothalamic neurons are resistant to 3-NPA that induces specific lesions in the striatum and hippocampus via the damage in the BBB.