The biliary output of carcinoembryonic antigen (CEA) in bile fistula rats following treatment with the microtubule poisons vinblastine and colchicine increased 3-fold over a 4-hr period. Cytochalasin B and the inactive colchicine derivative lumicolchicine had no effect. These treatments did not effect the rate of CEA clearance from the circulation. Biliary output of low molecular weight fragments from CEA degradation was decreased in the presence of colchicine and vinblastine. Mechanical obstruction of the bile duct for 3 days followed by relief of obstruction resulted in a 3-fold increased output of CEA into the bile. These results are consistent with a paracellular mechanism for CEA transport from blood to bile. Biliary duct obstruction and vinblastine and colchicine probably affect the permeability of junctional complexes between hepatocytes allowing CEA to penetrate more easily.