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Sanguinicolids, or fish blood flukes, infect the vascular system of both marine and freshwater fishes, and some act as serious pathogens of hosts in aquaculture. Blood flukes typically possess a relatively benign relationship with wild fishes; however, cultured hosts near appropriate intermediate hosts (i.e., snail, bivalve, or polychaete) may accumulate heavy infections of the worms and their eggs. The resulting disease, sanguinicoliasis, has caused mass mortalities of fish reared in ponds and cages in North America, Europe, and Asia. In the life cycle, the cercaria emerges from the intermediate invertebrate host and penetrates into and matures in the definitive fish host, and the resulting adult releases eggs into the fish’s vascular system. These eggs may be sequestered in gill, heart, kidney, liver, spleen, pancreas, or other organs, where they cause inflammation and decrease the physiological and mechanical efficiency of these organs. In some cases, they kill the host. Treatment of debilitated fishes is difficult, and the combination of stock destruction and facility disinfection is a realistic option for managing cases in freshwater systems. However, because this is usually not possible in marine systems, early detection and identification of the parasite, careful site selection and construction of culture facilities, and elimination of infected hosts (definitive or intermediate) are important. Much information needs to be acquired about each parasite’s biology and geographic range, and imported fishes and fish products should be quarantined or examined fresh for infections prior to potential contamination of culture systems.