Hemocytes constitute the cellular part of the mollusc immune system and are involved in phagocytosis; the production of toxic oxygen radicals, antimicrobial peptides, opsonizing molecules, and lysozymes; digestion, excretion, and nutrient transport. In this study, we investigated the phenotypic response, phagocytosis, and respiratory burst activity in hemocytes of Mya arenaria exposed to the bacterium Vibrio splendidus. Exposure to V. splendidus led to a loss of pseudopodia and rounding of hemocytes. The phagocytic ability of hemocytes was significantly reduced in challenged hemocytes, as was the respiratory burst activity of hemocytes. The expression of actin and elongation factor 2 genes was measured to investigate a possible relation between phenotypic response of hemocytes exposed to V. splendidus and genes associated with cytoskeleton. Both actin and elongation factor 2 genes were upregulated in challenged hemocytes. Additional studies are underway to identify other genes of hemocytes whose expression is affected by exposure to V. splendidus.