The southern flounder Paralichthys lethostigma is host to two species of philometrid nematodes in the estuarine systems of South Carolina, USA. Histologic studies showed that all worms were hematophagous and that the host-parasite interface varied according to the worm's location in the fish. Individuals of Philometra overstreeti associated with the teeth induced a degradation of the enameloid epithelium but elicited minimal host reaction, whereas those located in the branchial arches induced an intense inflammatory response. Individuals of Philometroides paralichthydis elicited no host reaction. Those associated with the bones of the buccal cavity were contained in a thick collagenous capsule, whereas those located between the depressor and erector muscles of each fin element displaced or thinned the fin inclinator muscles to the extent of eventually causing their complete atrophy. Often the bulk of gravid worms imposed upon uninfected adjacent fin element muscle groups. Damage induced by these worms are likely to affect feeding and swimming behavior of the infected flounder and thus, impact the population structure of this important fish species.