This research was initiated to determine the cause of oral papillomas on black bullheads (Ictalurus melas) from the final oxidation pond of theTuskegee, Alabama, sewage treatment plant. The water in this pond was chlorinated effluent from the sewage treatment plant. Ames-test mutagenicity of a pond-water concentrate indicated the presence of a chemical carcinogen in the pond water. However, water and sediment analysis did not identify substances suspected of causing the tumors. Cytoplasmic inclusion bodies were present in some papilloma cells. but attempts to find virions in the tumor via electron microscopy and to transmit the papillomas by means of injection of cell-free tumor homogenate into black bullheads were not successful. Juvenile black bullheads, yellow bullheads (Ictalurus natalis), and channel catfish (Ictalurus punctatus) were confined to cages in the oxidation pond and in a control pond. Most caged black bullheads in the oxidation pond developed focal, oral hyperplasia and stomatitis in the same mouth locations occupied by papillomas in wild black bullheads from this pond. These hyperplastic lesions healed in most fish during additional exposure. Mucosal hyperplasia also occurred, but at a much lower incidence, in other test species and in all control species. A similar incidence of hyperplastic lesions in black bullheads in floating and sunken cages indicated that contact with the sediment or ingestion of benthic food organisms did not affect pathogenesis of the lesion.