Allele frequencies of 28 genetic loci were determined in subsets (n ranged from 52 to 698) of a sample of Yupik-speaking Eskimos from southwestern Alaska. Five loci were monomorphic (Kell Kp(b+), ADA1, AK1, HBA, and PGDA). At the other loci, the most frequent alleles were ABO⁰ (0.580), Fya (0.960), Jkb (0.513), Ms (0.333), CDe (0.591), ACPA (0.566), ESD1 (0.890), GLO2 (0.736), GPT1 (0.653), Hp2 (0.654), PGM1 (0.836), PGP1 (0.972), and UMPK1 (0.873). The most frequent immunoglobulin allotype Gm(1;21) occurred with a frequency of 0.829. The HLA alleles that occurred with highest frequencies were A24 (0.626), Bw48 (0.184), Cw3 (0.404), and DR4 (0.329). The average heterozygosity at all loci was 0.423. Based on the presence of the European allotype, Gm3;23;5,11,13, the proportion of European admixture in the Eskimo population was estimated to be 2.1%.