Japanese pearl oysters (akoya oyster: Pinctada fucata martensii) are currently suffering mass mortalities from akoya-virus infection. In the present study, akoya oysters were injected with an anti-viral, recombinant feline interferon-ω (rFeIFN-ω) in an attempt to confer resistance to this virus. In infectivity experiments, oysters were twice injected with rFeIFN-ω at 1 mega unit kg -1 of the meat weight. They were challenged with a single inoculation of cultured akoya-virus and held for 20 to 30 d at 25°C. Control oysters received only the viral challenge without rFeIFN-ω administration. In prophylactic experiments, oysters that were given the akoya-virus on Days 1 to 5 after rFeIFN-ω administration showed lower mortalities. Furthermore, the survivors had fewer muscular lesions resulting from the virus infection than the controls. In treatment experiments, the virus was inoculated on Days 1 to 3 before rFeIFN-ω administration. None of the treated oysters died within a 30 d experimental period. Survivors displayed repaired lesions with fibrous tissues that were produced by enhanced agranulocytes in the body musculature. Moreover, rFeIFN-ω was not toxic to akoya oysters. Thus, rFeIFN-ω administration is efficacious in preventing mortality of akoya oysters with akoya-virus infection.KEY WORDS: Japanese pearl oyster · Akoya-virus infection · Recombinant feline interferon-ω · Efficacy in enhancement · Agranulocyte · Collagen fiber production Resale or republication not permitted without written consent of the publisher