Recently, Manila clam, Ruditapes philippinarum, populations have suffered mortalities in Arcachon Bay (SW France). Mortality was associated with extensive lesions of the posterior adductor muscle, which become progressively brown and calcified. Ultrastructural observations by transmission electron microscopy revealed tissue degradation with necrotized muscle fibres and granulocytomas. Unenveloped virus-like particles (VLPs) were detected in muscle, granulocytic, epithelial and rectal cells. VLPs were abundant in the extracellular space, in the cytoplasm (free or enclosed in vesicles) and in the nucleoplasm of granulocytes. Nuclei and mitochondria of granulocytes displayed changes which suggested reactive oxygen species production and apoptosis induction. VLPs exhibited an icosahedral structure with a diameter of 25 to 35 nm. These observations suggest that the VLPs could belong to the family Picornaviridae or the Parvoviridae.