At the Reeds Creek (West Virginia) state hatchery, mortality from enzootic furunculosis is most severe among brown trout Salmo trutta, intermediate in brook trout Salvelinus fontinalis, and virtually nonexistent in rainbow trout Salmo gairdneri. In each species, survivors of epizootics had developed similar levels of protective antibodies in their sera as demonstrated by microtiter agglutination and passive immunization experiments. We concluded that serum antibodies were not related to graded differences in resistance to furunculosis. These same fishes, however, produced a mucus precipitin that reacted with cell-free bacterial extracts in single-radial immunodiffusion assays. The mucus precipitin activity correlated with the resistance of the three species to furunculosis. Breeding studies with brown trout also showed that fish selected for a high level of mucus precipitin activity against Aeromonas salmonicida, the cause of fish furunculosis, produced progeny that were more resistant to furunculosis than other progeny produced from random matings. The nonspecificity of the mucus precipitin reaction was also confirmed by reactions with cell-free extracts from Vibrio anguillarum and Aeromonas hydrophila.