Abstract. To explore the effects of behavior and demography on balancing selection at major histocompatibility complex (MHC) loci, we examined allelic diversity at exon 2 of the MHC class II DQ locus in a social and a solitary species of tuco-tuco (Rodentia: Ctenomyidae: Ctenomys), both of which occur in the same valley in southwestern Argentina. By comparing patterns of diversity at this MHC gene to the diversity evident at fifteen microsatellite loci, we demonstrate that balancing selection at the DQ locus is enhanced in the social species compared to its solitary congener. These findings have intriguing implications for the role of behavioral and demographic parameters in maintaining diversity at MHC loci. Behavioral and demographic attributes may significantly affect patterns of genetic variation in natural populations of vertebrates (Hartl and Clark 1989;Ross et al. 1999). While interactions among behavior, demography, and genetic structure are well-documented for neutral genetic markers such as microsatellites (Nielsen 1997;Kimmel et al. 1998), the role of these variables in shaping variation at major histocompatibility complex (MHC) loci is considerably less well understood. Both molecular-and population-level patterns of allelic variation indicate that at least some MHC genes are subject to strong balancing selection (Hughes and Nei 1989; Edwards and Hedrick 1998). The functional role of these genes in the immune response, together with the discovery of specific pathogen-MHC allele interactions, suggests that pathogen exposure contributes to this selection (Hill et al. 1994;Paterson et al. 1998;Voeten et al. 2000). Because behavioral and demographic parameters are expected to influence pathogen exposure (May and Anderson 1979) as well as the movement of alleles within and among populations, variation in these parameters may also influence balancing selection and, hence, allelic variation at MHC loci.At the same time, behavioral and demographic factors may affect our ability to detect selection at MHC genes. Because these loci evolve within populations, they are subject to the same evolutionary forces (e.g., genetic drift) that shape variation at neutral loci. These forces, which are influenced by behavioral and demographic patterns, are expected to affect the impact of selection at functional loci (Hartl and Clark 1989). As effective population size decreases, the ability of natural selection to overcome the effects of drift is decreased (Kimura 1983;Li 1997). The effects of these forces may vary among populations, with the result that conspecifics in different populations may experience markedly different levels of selection on MHC loci, but these differences in selection may be difficult to detect unless patterns of neutral genetic structure are taken into account. Specifically, data from neutral markers provide a critical backdrop against which to 1 Present address: Centers for Disease Control, MS G-13, 1600 Clifton Road NE, Atlanta, Georgia 30333; E-mail: thambuch@ cdc.gov.evaluate the nature and i...