Serum specimens from 1385 unrelated males and females from seven Middle East and East European sample surveys (Prague, Olomouc, Krakow, Poznan, Szeged, Moscow, and Jekaterinburg) have been typed for seven polymorphic serum protein polymorphisms (GC, TF, PLG, PI, A2HS, F13B, and ITI). The distributions of phenotype and allele frequencies show a marked heterogeneity, especially with regard to the allel GC*1F of the GC system, the alleles A2HS*1 and A2HS*2 of the A2HS system and the alleles F13B*1 and F13B*3 allele of the F13B system. Analysis of the genetic variability by means of distance and principal component analysis revealed that with regard to the seven polymorphic loci studied the population samples from Prague and Jekaterinburg are characterized by deviating genetic structures. While the different genetic structure of the sample from Prague is mainly due to the distribution of the alleles at the A2HS locus, the sample from Jekaterinburg shows differences in several loci. The genetic dissimilarity corresponds to the large geographic distance from the other populations and can presumably be explained with the comparatively heterogeneous ethnic composition of the population of this city located at the geographic borderline between Europe and Asia.