Histamine, a vasoactive mediator, may play a role in the pathogenesis of neonatal hypoxic-ischemic cerebral injuries. We have previously found that histamine accumulated in brain compartments during asphyxia (Kovácset al. 1995 Neurosci Lett 195:25), and antihistamines prevented brain edema formation (Dux et al. 1987 Neuroscience 22:317) in asphyxiated newborn pigs. The aim of the study was to reveal the changes in the blood-brain barrier (BBB) permeability after the intracarotid injection of histamine. Thirty newborn pigs (4-8 h; 1,180-1,530 g; ketamine anesthesia, 10 mg × kg-1) of either sex were included in the study. The left internal carotid artery of the animals was catheterized through the external branch, and histamine diluted in 1.0 mL isotonic saline was injected into the vessel in the following doses: 0, 10-6, 5×10-6, 10-5, 5×10-5, 10-4 M, respectively, through 1 min in 6 groups of animals (n=5 in each). Then the external carotid artery was ligated, and 1 h after the challenge BBB permeability was determined concomitantly for a small (sodium fluorescein, SF, 376 Da) and a large (Evans blue/albumin, EBA, 67 kDa) tracer (2%, 5 mL×kg-1, 30 min circulation time for both dyes) in frontal, parietal and occipital cortex, hippocampus, and periventricular white matter both on left and right sides. After the removal of the intravascular dyes by perfusion, the BBB permeability for both tracers was quantified by fluorescence spectrophotometry, the wavelengths for excitation and emission were 440 nm and 525 nm for SF; and 620 nm and 680 nm for EBA, respectively. Histamine injection in doses higher than 10-6 M resulted in a significant (P<0.05; Kruskal-Wallis one way ANOVA on ranks followed by Dunn's test) increase in BBB permeability for both tracers in each brain region examined. Changes in the left hemisphere were more intense (P<0.05) than those in the right one after the doses of 5×10-6 and 10-5 M in each region, while 10-4 M histamine administration induced similar edema in both sides. We conclude that intracarotid histamine infusion results in a dose-dependent vasogenic brain edema formation in newborn pigs.