Tilapia mossambica maintained at high densities in an intensive‐culture tank system displayed hypersensitivity to a component present in mucus and culture water. The component induced cutaneous anaphylactic reactions in T. mossambica and three other Tilapia species, but did not affect Ictalurus punctatus. Gel filtration studies revealed the component to be high molecular weight (larger than 8 × 105 daltons) which electrophoretically migrated as a beta globulin. The component recovered from tank water of T. mossambica was not found in T. aurea tank water or in the incoming water. Tilapia mossambica experience higher mortality due to this autoimmune reaction, which limits the density at which this species can be stocked. Because the compound affects several species within the Tilapia genus, its effects should be considered when tilapias are stocked in fish culture operations.