Background Previous (incomplete) data suggested that P might modify B metabolism in brain1,2. This is potentially important, as P is still in use for treatment of hyperbilirubinemia. Materials/methods We have studied the clearance of B from brain following pretreatment of young adult SPRD rats with P 75 mg/kg ip daily for 7 days, controls received solvent only (n=8 in each group). On day 8 rats were anesthetized and 50 mg/kg B was infused iv over 5 min. Rats were sacrificed after 60 min, the brain vasculature flushed in situ, and brain B determined by acid chloroform extraction. Serum B at sacrifice was determined by a diazo method. Results As expected following P treatment, serum B was slightly lower in P-treated vs control rats(126±32 vs 140±21 μmol/L, p=0.3). Brain B values were also lower in the P-treated rats (0.52±0.08 vs 0.44±0.06 nmol/g, p=0.044). As the lower brain B values in P-treated rats could be due entirely to lower serum B values, we compared the brain: serum B ratios in the two groups and found these to be identical (0.0037). Conclusion P does not directly affect metabolism of B in rat brain. The 60 min time point for sacrifice represents at least 3 half-lives of B in brain, thus brain B concentration at this time is a good proxy for clearance. We speculate that P treatment may be neither helpful nor harmful relative to the neurotoxic effects of B in infants with already established jaundice.