Three strains of specific pathogen-free (SPF) oysters (Crassostrea virginica) were set on shell and deployed on 3 oyster bars along a salinity gradient in the Patuxent River, MD, to determine whether oyster strains selected or bred for enhanced disease tolerance would outperform a generic control strain in survival and/or growth while under pressure from Perkinsus marinus (the agent of dermo disease). A local Standard oyster strain was used as a reference control, and selected oysters belonged to disease-tolerant DEBY and CROSBreed strains. Initial deployment was in September 2003, during a period of unusually low salinity. Mean river salinities during the first 2 y were 8.5‰ and 9.0‰, respectively, but these rose to historically typical levels of 11.5‰ and 11.3‰ during the third and fourth years. Although measuring possible differential effects of dermo disease pressure on the 3 strains was our primary goal, disease pressures were only slight or moderate during all but the final year of the study. Oysters grew well during most of the study, except at the upriver station, where salinities were less than 5‰ during much of the first year. The DEBY strain showed the best overall growth and survival. Standard and CROSBreed strains were similar in both growth and survival, and did not perform as well as DEBYs. Although P. marinus infection prevalences approached 90–100% among oysters at the 2 downriver sites, even during the first year, and were generally high in late summer each year, oyster body burdens of pathogen cells increased slowly throughout the study, with means reaching lethal levels of 10⁶ parasite cells/g tissue only among Standards and DEBYs, and only during the fourth year. P. marinus infections among sympatric feral oysters (the probable source of disseminated cells infecting SPF oysters), were low during all years at the upriver site, but increased each year with increasing salinities at the downriver sites. As measured by better growth and survival, DEBYs performed best among the 3 strains tested. Whether DEBYs have a use in oyster restoration efforts is controversial, but their value in aquaculture applications appears evident.