The ability to identify individual isolates of Entamoeba histolytica Schaudinn 1903 (Emend. Walker 1911) is necessary before several important epidemiological questions can be answered. We have developed such a method based on our discovery of extensive polymorphism in two E. histolytica genes--the serine-rich antigen gene and the "strain specific gene"--each of which has an internal tandemly repeated structure. Using the polymerase chain reaction we detected both size and restriction site polymorphisms in the repetitive regions. When the two genes were used in combination we obtained 16 distinct DNA patterns out of 18 isolates examined. Moreover, these patterns proved to be stable under a variety of conditions--long-term culture, axenization, cell cloning, and animal passage.