We have studied the entry of 3H-bilirubin and 125I-albumin into brain regions in young rats during short-term (1 h) hyperbilirubinemia. Bilirubin enters the brain both under control, displacer (sulfisoxazole 50 mg/kg), hypercarbic (PCO2 18-21 kPa; pH approximately 6.9), and hyperosmolar (serum osmolality approximately 400 mosm/l) conditions. No significant differences in bilirubin uptake were found between brain regions. Thus preferential staining of basal ganglia ('kernicterus') may not be a phenomenon related to uptake. Albumin does not cross the blood-brain barrier under control or displacer conditions, but does enter the brain to some extent in hypercarbia, and to a greater extent in hyperosmolality. During control and displacer conditions, only unbound bilirubin appears to enter the brain. In hypercarbia bilirubin enters primarily in the unbound form, but some is also albumin-bound. In hyperosmolality a significant fraction of the bilirubin entering the brain is albumin-bound.