We report a case of hyperphosphatasemia in a 35-year-old patient with hepatitis B who underwent an orthotopic xenogeneic liver transplant. Marked increases in total alkaline phosphatase (ALP; EC 3.1.3.1) activity began 5 days posttransplantation (six times human normal) and increased to approximately 17 times normal at day 11. Increased ALP persisted for > 40 days and steadily increased to 75 times normal in the patient's last 30 days. Gel electrophoresis detected both liver (LALP) and biliary (high-molecular-mass, BALP) isoforms. LALP measured with ion-exchange columns revealed an activity time course pattern similar to that of total ALP. Results for BALP activity also obtained with ion-exchange columns exhibited broad variability, ranging from 2 to 428 times normal.