Tumor necrosis factor alpha (TNF alpha) plays a significant role in the pathogenesis of central nervous system infections. We investigated the effect of intracisternal injection of recombinant human TNF alpha (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. TNF alpha may be involved in the pathophysiology of neonatal brain injuries.