A series of 1,187 blood samples from eight population groups in the Eastern Highlands of Papua New Guinea were tested for genetic variation in blood groups, serum proteins and red cell enzyme systems. The populations belonged to the language groups Gahuku-Asarc-Bena Bena, Kamano, Yagaria, Keiagana, Fore, Agarabe, Auyana and Tairora. Polymorphic variation was found in the ABO, MNS, P1; Rh, Hp, Tf, SEP, 6-PGD, ADA, MDH, and PGM genetic systems. East to West variation was shown in the language groups; the O, S, R2, and R₀ genes increase in frequency from East to West and the A, R1, and M genes decrease in the same direction. In the East higher frequencies were found for the Da antigen, for the PGM21 gene and for a PGM second locus variant. The MDH 3 variant was found in all the populations, its highest value being in the Tairora.