Innate immunity is the initial response of a host in defending against pathogen invasion (Beutler 2004, Janeway and Medzhitov 2002). The key features of an innate immune response are that it is: non-specific (broad-spectrum), rapid (often within minutes to hours) and conserved in its pattern of recognition. Antimicrobial polypeptides (AMPP) are a key component of the innate system and present in virtually all life forms (Zasloff 2002). One of the most widespread AMPP in fish are the piscidins. Piscidins have potent, broad-spectrum activity against viruses (Chinchar et al 2004), bacteria (Silphaduang and Noga 2001), fungi (Lauth et al 2002) and parasites (Colorni et al, Accepted). Another family of AMPP are histone-like proteins (HLPs), which are highly homologous to core nuclear histones (Robinette et al 1998, Noga et al 2002). Because disease is often the major cause of economic losses in fish farming, understanding how stress affects innate immunity (e.g., expression of AMPP) and thus disease susceptibility could be highly beneficial to the industry. One very important factor that can contribute to stress in aquaculture is inadequate nutrition. Feed is the single largest expenditure in semi-intensive and intensive farms (Lunger et al 2007, Twibell et al 2003, Mbahinzireki et al 2001). Thus, reducing feed costs while still maintaining optimal health is critical for successful production. As nutrient intake decreases, metabolic processes are impaired and susceptibility to disease increases. I anticipated that this would be reflected in the levels of piscidins and HLPs. The overall goal was to investigate the levels of these antibiotics that indicate fish are stressed prior to any pathological signs. For this first, an ELISA for piscidin 4 was developed and validated and its application to assess stress was confirmed. Using this ELISA and various other independent assays the presence of piscidin 4 related AMPP were detected in important aquacultured fish. Next, I found that nutritional deprivation has a deleterious effect on piscidin 4 expression and that susceptibility to an ich increases in hybrid striped bass ( Morone saxatilis [male symbol] x M. chrysops [male symbol]). The nutritional deprivation also lead to dermatological condition in channel catfish.