Abstract Tumor necrosis factor α (TNFα) plays a significant role in the pathogenesis of central nervous system infections. We investigated the effect of intracisternal injection of recombinant human TNFα (50–50,000 IU) on pial vasoreactivity and blood-brain barrier permeability in newborn piglets. The cytokine administration resulted in arterial vasoconstrictions, blood-brain barrier opening for Na-fluorescein (mol. wt. 376 Da) and increased Na-fluorescein uptake in brain regions examined (parietal and occipital cortex, cerebellum, pons/medulla, periventricular white matter) in a dose-dependent manner. TNFα may be involved in the pathophysiology of neonatal brain injuries.