We examined genetic variability and spatial heterogeneity of a class-II locus of the major histocompatibility complex (MHC) for 7 populations of white-tailed deer (Odocoileus virginianus) from Iowa, New York, Oklahoma, and Tennessee. Although white-tailed deer east of the Mississippi River have experienced drastic population reduction, all populations exhibited high levels of allelic diversity and all but 2 pairwise comparisons exhibited evidence of significant population divergence. These results suggest that previous bottlenecks have not drastically reduced Mhc-DRB allelic diversity in white-tailed deer.