Cutaneous and lower gastromtestinal (GI) tract mucus of rainbow trout Oncorhynchus mylclss were evaluated for inlmunological responses followvlg exposure to infectious hematopoietic necrosis w u s (IHNV) Juvenlle rainbow trout (mean weight 5 4 g) were infected w~t h IHNV (isolate 220-90) by waterborne exposure to 104 plaque formmg u n~t s (pfu) m1 ' or by a n inlection challenge of 104 pfu fish-' Cutaneous mucus and lower G1 tract washings were analyzed for vuus neutrahzing achvity (antiviral achvlty) usmg a complement-dependent neutrahzation procedure Antivual achvlty was pnrnanly detected in the G1 tract and was highest in mock mfected fish (not exposedrto w u s ) T h s activity decreased rapidly over time in fish challenged by the injection route Specific antibodes were not detected in cutaneous mucus or G1 tract washings by ELISA Virus was isolated in external and G1 tract mucus from both waterborne and injection challenged fish, and showed significantly h g h e r hters in fish challenged by the inlection route Histological exarmnation of fish exposed to IHNV showed a moderate inflammatory response in the mucosal ep~thehal layer of the skin ulth mmor focal areas of cellular necrosis in severely infected fish When the study was repeated m addltion to cutaneous mucus and G1 tract washings, serum was monitored for antibody production m juvenlle ralnbow trout (mean weight 2 4 g ) out to 28 days post-exposure (dpe) Anlviral activity was confirmed m the G1 mucus, and virus neutrahzing antibodies were detected in the serum at 21 and 28 dpe in IHNV challenged fish Anhbodies in slun and G1 mucus were not detected by ELISA Virus antigen was vlsuahzed by unrnunoh~stochemistry in the ludney spleen hver heart pancreatic tissue and smooth muscle of the stomach wall Results from these expenments reveal innate mechamsms of viral resistance w h c h may be unportant as a first line of defense against IHNV