AbstractWe assessed the bilirubin reduction capacity of three different types of devices in vitro: a high‐permeable membrane column for double‐filtration plasmapheresis (DFP) (Evaflux 2A, Kuraray, Japan), and non‐coated charcoal column for hemoperfusion (HP) (N‐180, Asahi Medical, Japan), and ion‐exchange columns for plasma adsorption (PA) (BR‐350, Asahi Medical, Japan, and B‐001, Kuraray, Japan). A column for DFP reduced the concentration of lowmolecular proteins effectively such as plasma bilirubin and bile acids in an albumin‐dependent manner. A charcoal column adsorbed low‐molecular substances preferentially. But in these two columns, the loss of fibrinogen is a limiting factor for determining the processing plasma volume. Ion‐exchange columns for PA adsorbed bile acids, disconjugated bilirubin, and monoconjugated bilirubin more efficiently compared with delta‐bilirubin and unconjugated bilirubin. Pretreatment of the column with heparin reduced the loss of fibrinogen to less than 10%. We applied the BR‐350 ion‐exchange column in vivo for treatment of three patients with hyperbilirubinemia. After treatment, an alcoholic hepatitis patient with the hepatorenal syndrome (HRS) recovered from acute renal failure. However, in a patient with primary biliary cirrhosis and in a patient with fulminant hepatitis, the decrease of serum bilirubin was transient and no obvious beneficial responses were noted. The capacity and ability of the BR‐350 column to adsorb plasma bilirubin was shown sufficient to treat deeply jaundiced patients, because 4 liters of the plasma of a patient with 108 mg/dl of initial total bilirubin concentration was able to be processed continuously without an obvious decrease in bilirubin adsorption capacity. Therefore, this column in combination with dialysis may be most applicable in lowering serum bilirub