The regulation of genetic variation in natural populations is via both neutral and selective processes. Signatures of the neutral processes of drift and gene flow can be found within non-coding regions of the genome, while natural selection acts on variation within coding genes that confer changes in fitness. The affects of neutral and selective processes are examined in thinhorn sheep (Ovis daW spp), a rare example of a North American large mammal that occupies most of its native range. There are currently two recognised thinhorn subspecies (0. d. daW and 0. d. stone i), the validity of which remains uncertain. Microsatellites reveal significant genetic structure throughout the thinhorn species range (FsT=0.16). At least eight regional genetic groups can be defined, the limits of which are delineated by mountain range topology. Strong isolation-by-distance is evident (r=0.75, P < O.OOI), suggesting limited dispersal and philopatry within the species. Analysis of mitochondrial DNA reveals that sheep survived Pleistocene glaciations in four refugia. In addition to the well known refugia of eastern Beringia and areas south of the Laurentide and Cordilleran ice sheets I show evidence of two smaller refugia, providing support for the presence of the disputed 'ice-free corridor' through eastern British Columbia. MtDNA also reveals a genetic signal confirming the past hybridization of thinhorn and bighorn sheep. Patterns of variation in linked microsatellite loci show no evidence of natural selection acting on three genes involved in the thinhorn immune region. Although Watterson tests suggest balancing selection is acting in all genes, evidence for selection is confounded by popUlation structure. Concordantly, the translated coding sequences of thinhorn interferon gamma, natural resistance associated macrophage protein and prion protein have low genetic diversity. In contrast, the major histocompatibility complex locus DRB3 shows significant evidence of overdominance through both an excess of nonsynonymous substitution and transspecies polymorphism.