Because of its sensitivity to disturbances of excretory liver function, gamma-glutamyltransferase (GGT; EC 2.3.2.2) assay has become one of the most important diagnostic tests for hepatobiliary disorders. However, its value in the differential diagnosis of liver diseases is limited. It is present in kidney, liver, pancreas, and intestine in electrophoretically distinct but not necessarily organ-specific forms. Much effort has been expended to relate diseases of these organs to isoenzyme findings in serum. Although the activities of GGT isoenzymes in disease differ from those in health, the existence of disease-specific patterns is controversial. Much is known about the biochemistry, structure, and immunochemistry of GGT, but more work is needed on methods, standardization of terminology, and correlation of isoenzyme findings with diseases. Further progress in the last area should improve the clinical applicability of the isoenzyme activities.