The changes in serum alkaline phosphatase that are of main diagnostic importance result from increased entry of enzyme into the circulation. This results from increased osteoblastic activity in bone disease, and increased synthesis of alkaline phosphatase by hepatocytes in hepatobiliary disease. The liver and bone forms of alkaline phosphatase are differently-glycosylated forms of a single gene product. The main value of their specific estimation is found in patients in whom bone and liver diseases co-exist, for example, as a result of cancer. Abnormal expression of genetically-distinct alkaline phosphatase isoenzymes is valuable in monitoring cancers, particularly germ-cell tumors. These isoenzymes include Regan and Nagao isoenzymes, which correspond respectively to normal placental and placental-like alkaline phosphatases, and the Kasahara isoenzyme which appears to result from re-expression of a fetal intestinal alkaline phosphatase gene.