We studied the prevalence and intensity of the parasitic copepod Myicola ostreae in 2 closely related oysters Crassostrea angulata and C. gigas and their F1 hybrids. The effects on host and host reaction were also analysed to better understand host-parasite relationships between copepods and bivalve molluscs. Full reciprocal crosses were carried out between C. angulata and C. gigas and the progenies were reared in the wild in Ria Formosa Lagoon (Portugal), allowing natural infestation by M. ostreae. Prevalence and intensity were significantly higher in C. angulata than in C. gigas. The parasite level of F1 hybrids was similar to C. angulata and significantly higher than in C. gigas. The results of our study support a hypothesis of dominantly inherited susceptibility to M. ostreae infestation. Moreover, copepods were observed on the gill surface of C. gigas engulfed by a capsule-like structure. Histological analyses revealed that the copepods were surrounded by a massive agglomerate of haemocyte-like cells encircled by a thin layer of fibroblast-like cells. This encapsulation response was not observed in C. angulata or in F1 hybrids. These results suggest that the differential susceptibility to M. ostreae between C. angulata and C. gigas may be ascribed to host defence factors.