Epizootic shell disease (ESD) is a degradative process of the carapace in the American lobster, (Homarus americanus), putatively caused by bacterial infection, and potentially responsible for serious economic losses to the lobster fishery. In Long Island Sound (LIS), ESD is prevalent in lobsters from eastern LIS (ELIS), but almost absent in western LIS (WLIS), presenting a unique opportunity to examine the influence of microbial communities on the disease process among these subpopulations. Bacterial community compositions in diseased shell, healthy shell subsamples from lobsters exhibiting signs of disease, and carapace subsamples of healthy lobsters from ELIS, WLIS, and a coastal Maine reference site were profiled using terminal restriction fragment length polymorphism (TRFLP). Although overall bacterial community membership in diseased shell was not significantly different from healthy shell and healthy lobsters, prevalence of some individual terminal restriction fragments (TRFs) varied among disease state. Several TRFs were more abundant within lesions, whereas representation of other members appeared to be diminished, particularly members of the β- and γ-proteobacteria. One TRF linked to anaerobic bacteria was enriched in lesions, suggesting anoxic microenvironments within diseased tissues. Activities of 4 ectohydrolases among communities were also measured in replicate excised shell samples. Chitinase potentials were high in all samples, and were indistinguishable among sample types. In contrast, proteinase and cellulase potentials were significantly higher in diseased shell than healthy shell and healthy lobster. Lipase potentials in LIS samples were significantly higher than those from Maine, but similar among disease states. The absence of site-specific differences in microbial communities suggests that biogeographic variation in colonizing microbes is not a factor in disease susceptibility. Lesion development appears to induce compositional shifts in normal carapace microflora, with displacement of some community members as others become more prevalent. Protein and cellulose appear to be more important targets than chitin for bacterial degradation within lesions. Furthermore, lipase activity, degrading the epicuticle lipid layer, may play a key role in regions with high disease prevalence.