This research was initiated to determine the cause of the oral papillomas on black bullheads (Ictalurus melas) from the final oxidation pond of the Tuskegee, Alabama, 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 using electron microscopy and to transmit the papillomas by 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. Caged fish did not develop neoplasms but 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.