Understanding the selective forces influencing genetic diversity is a fundamental goal of evolutionary ecology. The genes of the major histocompatibility complex (MHC) play a key role in the adaptive immune response of vertebrates and thus provide an excellent opportunity to examine the agents of selection on a functionally important gene. Here we examine the genetic architecture of the MHC class IIB genes in 10 wild populations of guppies (Poecilia reticulata) in Northern Trinidad. We have previously shown that these populations are significantly less diverged at the class IIB locus than expected based on neutral (microsatellite) loci. We now survey infection by Gyrodactylus turnbulli and G. bullatarudis, common parasitic worms that infect guppies, as a potential agent of homogenizing selection. We used a genetic algorithm to partition both additive and non-additive genetic effects of the five most common MHC allele types as well as a rare allele category. Although we found no evidence for non-additive effects, across the populations we found that one allele type (the a-type) had a significant negative additive effect on parasite load. Thus, individuals who had more copies of the a-type allele were infected with fewer gyrodactylus than individuals with fewer copies of the allele. These results not only link parasite infection with MHC genotype, they provide a mechanism of homogenizing selection across these otherwise disparate populations.