Background: A considerable body of data has been accumulated since the 1960s on protein electrophoretic markers in the Jewish populations of Israel. However, in some Jewish communities and for some markers insufficient information has been available. In addition, studies that tried to explore the genetic affinities of various Jewish populations mainly employed antigenic markers and frequently used a small and unrepresentative number of non-Jewish populations as comparisons. Aim: The primary objectives of the present study were to create a comprehensive database for protein electrophoretic markers in Israel and thereby to explore the genetic affinities of different Jewish populations. Subjects and methods: Published information on red cell enzyme and serum protein polymorphisms in Israeli Jewish populations was combined with new data obtained by protein electrophoresis and DNA PCR (polymerase chain reaction) methods to create the database. The genetic affinities were investigated by two methods. Ten Jewish populations were classified in a discriminant analysis based on nine markers and 65 non-Jewish populations. The same markers and populations were also used in a genetic distance analysis. Results: The database contains new information on 15 protein electrophoretic markers in 14 Israeli populations, including three Jewish populations from Turkey, Tunisia and the Caucasus region, for which no or only scarce data were previously available. The discriminant analysis resulted in only two Jewish populations, from Iraq and Yemen, being classified within the Middle Eastern group. According to their genetic distances, no particular genetic similarity was observed between the various Jewish study populations. Conclusions: In contrast to the conclusions of several previous studies, there was no evidence for close genetic affinities among the Jewish populations or for a Middle Eastern origin for most of them. Since the study is the first to use only the more reliable protein electrophoretic markers, and an appropriately comprehensive panel of non-Jewish populations, the results are regarded as the most reliable available to date.