Balancing selection maintains high levels of polymorphism and heterozygosity in genes of the MHC (major histocompatibility complex) of vertebrate organisms, and promotes long evolutionary persistence of individual alleles and strongly differentiated allelic lineages. In this study, genetic variation at the MHC class II DAB-beta1 locus was examined in 31 populations of sockeye salmon (Oncorhynchus nerka) inhabiting the Fraser River drainage of British Columbia, Canada. Twenty-five percent of variation at the locus was partitioned among sockeye populations, as compared with 5% at neutral genetic markers. Geographic heterogeneity of balancing selection was detected among four regions in the Fraser River drainage and among lake systems within regions. High levels of beta1 allelic diversity and heterozygosity, as well as distributions of alleles and allelic lineages that were more even than expected for a neutral locus, indicated the presence of balancing selection in populations throughout much of the interior Fraser drainage. However, proximate populations in the upper Fraser region, and four of six populations from the lower Fraser drainage, exhibited much lower levels of genetic diversity and had beta1 allele frequency distributions in conformance with those expected for a neutral locus, or a locus under directional selection. Pair-wise FST values for beta1 averaged 0.19 and tended to exceed the corresponding values estimated for neutral loci at all levels of population structure, although they were lower among populations experiencing balancing selection than among other populations. The apparent heterogeneity in selection resulted in strong genetic differentiation between geographically proximate populations with and without detectable levels of balancing selection, in stark contrast to observations at neutral loci. The strong partitioning and complex structure of beta1 diversity within and among sockeye populations on a small geographic scale illustrates the value of incorporating adaptive variation into conservation planning for the species.