The 4 species of phocid pinnipeds that live in pack-ice habitats of the Antarctic have been relatively isolated from infectious diseases that are prevalent in mammals elsewhere. Consequently, patterns of genetic variability at key immune system loci in these seals might be primarily related to other selective factors correlative with interspecific differences in life history, demography, and ecological niches. To test that hypothesis, we investigated nucleotide-sequence variation in a 162-base pair region of DQα exon 2 in major histocompatibility complex (MHC) class II genes of Weddell seals (Leptonychotes weddellii), crabeater seals (Lobodon carcinophaga), Ross seals (Ommatophoca rossii), and leopard seals (Hydrurga leptonyx) from the Ross Sea of Antarctica. We found substantial differences in patterns of population genetic diversity among these seals. Crabeater seals were the most diverse, with 2 DQα loci, 39 distinct alleles among 30 seals, and at least 93% observed heterozygosity. Leopard seals were the least diverse, with only 1 allele detected in 13 seals. Weddell and Ross seals had intermediate diversity, with 11 alleles in 35 Weddell seals (89% observed heterozygosity) and 2 alleles in 42 Ross seals (21% observed heterozygosity). These patterns are congruent with extant knowledge of interspecific variation in life histories, population biology, and ecological niches of these species and consistent with previously reported patterns of microsatellite genetic variability. Moreover, our findings suggest that responses to past evolutionary pressures have differed in each species and that interspecific variation in future responses to introduced infectious diseases also may vary substantially.