ABSTRACT— Cellular immune reactions against normal biliary tract antigens have been investigated in 21 patients with primary biliary cirrhosis (PBC) and 18 with chronic active hepatitis (CAH) using the leucocyte migration inhibition test with partially purified antigens from normal human gall-bladder bile. Four antigen fractions, containing (either separately or together) three previously-described biliary antigens, were employed: (1) Antigen I; (2) Canalicular antigen; (3) Canalicular and Ductular antigens; (4) All three antigens. Seventeen (81%) of the PBC patients showed migration inhibition with all four fractions. Five (28%) of the CAH patients showed inhibition with three fractions but none exhibited sensitization to the fraction containing only the antigen derived from the bile canalicular portion of the hepatocyte membrane. In experiments with purified lymphocyte sub-populations from PBC patients, leucocyte migration inhibitory factor production was shown to be a function of T-lymphocytes. The antigenic selectivity with respect to the responses in CAH patients suggests that sensitization to biliary tract antigens is probably not a secondary phenomenon resulting from »unmasking« of antigens after bile duct damage has occurred but may be more directly related to the disease process.