Vesicomyid clam species are abundant in many deep-sea chemosynthetic communities, including cold seeps. They rely primarily on thiotrophic (sulphide-oxidizing) gill symbionts for nutrition and thus require sulphide-rich environments. Submersible surveys of megafaunal distributions at the Blake Ridge Diapir, a deep-sea methane-hydrate seep located ∼200 miles off the coast of Charleston, South Carolina, documented massive mortalities of vesicomyid clams. The cause of these mortalities is unknown, but sulphide deprivation, sulphide toxicity, and disease are possible agents of mortality in this system. Similar redox profiles in sediment cores from live and dead clam beds do not support the hypothesis that there has been a transient shift in the flux of sulphide. To address the potential for disease as a cause of mortality, we undertook a histological survey of microparasites and other indications of disease in clam tissues. Six morphological types of parasites were identified using light microscopy, including two viral-like inclusions, Rickettsia-like gill inclusions, possible bacterial gut inclusions, bacterial gill infections, and a protistan inclusion. Of these parasites, two were pathogenic: viral-like inclusions in mantle tissues caused tissue degradation; bacterial gill infections resulted in localized disruption and degradation of gill filaments. Infection prevalence and densities were low for all parasites observed. The majority of clams examined showed intense haemocytic responses in the absence of any obvious etiologic agent, suggesting the presence of parasites not detectable by our methods. Our findings indicate that the clam population at the Blake Ridge seep was in relatively good health at the time of sampling.