Abstract: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, which predominantly affects women. It is characterised histologically by necroinflammation of small intrahepatic bile ducts and biochemically by elevated serum alkaline phosphatase, levels of which at diagnosis predict survival. Ursodeoxycholic acid (UDCA) is the only treatment shown to improve liver biochemistry and survival. We report two patients with PBC who show a fall in serum alkaline phosphates levels whilst receiving tamoxifen therapy. Tamoxifen may exert this effect, which warrants further study, either via cholangiocyte estrogen receptors, inhibiting cholangiocyte proliferation and inducing apoptosis or by activating pregnane X receptor, analogous to the mode of action of UDCA.