Background Entry of B into brain is enhanced by inhibition of PGP in the BBB. The mechanism for distribution of B to the basal ganglia(kernicterus) is not known. We postulated that pretreatment with ceftriaxone, a drug known to inhibit PGP, would alter the regional distribution of B in brain in a pattern corresponding to kernicterus. Materials and methods Young adult Sprague-Dawley rats (n=10 in both groups) were anesthetized and pretreated with an IV bolus dose of ceftriaxone 100 mg/kg or an equivalent volume of saline (controls). 10 min following the drug injection the rats received a 5-min bolus dose of 50 mg/kg B with ≅20 μCi of3 H-B. The rats were killed 5 min after the end of the B infusion, and the brain blood vesels were flushed in situ. Brain B was determined by scintillation counting. Results were compared with two-way ANOVA. Results The mean serum B concentrations for the control and drug-treated groups at sacrifice were 618±73 and 535±43μmol/L respectively (mean ±SD, p=0.006). Brain B concentrations were significantly higher in brain regions from the drug-treated rats than the controls (F=114.2, p<0.0001). In both groups there were significant differences in B concentrations between brain regions (F=9.5, p<0.0001). However, in both groups this was primarily accounted for by a higher concentration in the cerebellum, and the distribution of B between regions was not different between controls and ceftriaxone-treated rats. Discussion Inhibition of BBB PGP function by ceftriaxone significantly increased the acute influx of B into brain, but did not change the regional distribution relative to control conditions. The expression of PGP in the BBB increases with postnatal age. Further studies will be needed to address the question of whether there may be differences between brain regions in the rate of maturation of BBB PGP function.