In this study of short-term exposure of Ruditapes philippinarum from Brittany, France, to an Alexandrium tamarense isolate that produces high concentrations of paralytic shellfish toxins (PSTs), the effects of the isolate on clam fitness, toxin uptake, and the response of hemocytes (responsible for internal defense in bivalves) were examined. Adults exhibited individual variability in resistance to the effects of PSTs, measured by their burrowing capacity. If genetically based, this may (1) indicate that resistance is under natural selection and (2) provide a new model to advance our understanding of the molecular basis for PST resistance in bivalves, so far determined only in Mya arenaria. Juvenile clams were more vulnerable to PSTs than adults, experiencing 100% burrowing incapacitation within 1 d of exposure to A. tamarense. They also experienced growth suppression and high mortalities following 4 d of toxification. Juveniles challenged with Vibrio tapetis, the cause of brown ring disease (BRD), and exposed to A. tamarense, developed significantly fewer BRD symptoms relative to controls fed non-toxic algae, but suffered higher mortality. Adult clams exposed to A. tamarense showed a significant increase in hemocyte concentrations and a small, but significant, decrease in phagocytic activity, and no effect on hemocyte viability or other functional parameters. We speculate that the inhibitory effects on BRD progression may be attributable to toxicity of PSTs to V. tapetis, inability of juveniles to activate the shell conchiolin-deposition response, and/or an overall increase in phagocytic cells induced by A. tamarense. Harmful algae and pathogens may thus interact and modulate the effects of disease in bivalve populations.