The ability of pathogens to neutralize host defence mechanisms represents a fundamental requisite in the successful establishment of an infection. Host-pathogen interactions between quahog parasite unknown (QPX) and its hard clam host are poorly understood. Our prior in vivo investigations have shown that different QPX isolates display varying levels of pathogenicity toward clams. Similarly, field investigations and laboratory transmission studies revealed some variations in the susceptibility of different hard clam stocks to QPX infection. An in vitro approach was developed in this study to evaluate the toxicity of QPX cells and extracellular products toward haemocytes using a neutral red uptake assay. Results demonstrated that QPX produces virulence factors that are cytotoxic to M. mercenaria haemocytes. This cytotoxicity appears to be induced by clam factors, suggesting that it may play an important role in supporting QPX infection and proliferation within the host. Moreover, application of this technique to different QPX isolates and clam broodstocks indicates variations of QPX cytotoxicity in agreement with previous in vivo experiments, strengthening the existence of different QPX strains.