DescriptionDermo is a lethal disease of the eastern oyster Crassostrea virginica (Gmelin), and causes widespread mortality throughout most of its range. The pathogen is a protozoan parasite, Perkinsus marinus (Levine 1978). Despite its impact on oysters, there is little evidence demonstrating the development of resistance in wild oyster populations. On the island of Martha’s Vineyard off the coast of Massachusetts, four wild oyster populations inhabit separate coastal ponds with varying histories of P. marinus exposure. Two complementary studies were performed using these oyster populations to evaluate responses to Dermo disease: one study monitored disease levels to detect phenotypic response, and the other assessed genotypic differences that are the result of natural selection following disease exposure. The first study tested the hypothesis that different patterns and levels of Dermo disease correlated to exposure history. Disease prevalence and intensity were monitored using Ray’s Fluid Thioglycollate Medium (RFTM) assay during the 2008 and 2009 summer seasons. One population remained uninfected. The infected populations experienced different patterns of Dermo that indicated the influence of factors such as salinity, water temperature, and the breaching of barrier beaches separating the ponds from the ocean, but did not correspond to exposure history. The second study used putatively neutral and Dermo resistance-linked microsatellite markers to test the hypothesis that genetic divergence from the uninfected control population increases with duration of Dermo-mediated selection. Polymerase chain reaction (PCR) was used to genotype the oysters for both types of markers. Population analysis with resistance markers revealed a general increase in divergence of infected populations from the unselected population over time, whereas neutral markers showed little divergence and no correlation with Dermo exposure history. One pairwise differentiation with the resistance markers, however, showed no correlation to selection time, suggesting that the influence of other factors on selection dynamics can be important. This research indicates that, while wild oyster populations may develop genetics-based resistance to Dermo disease with time, there are many biological and physical factors that may alter the realization of disease resistance.