We 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 low-molecular 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.(ABSTRACT TRUNCATED AT 250 WORDS)