To better characterize neoplasm epizootics in the Great Lakes basin and their association with families of contaminants, we sampled five locations: the Fox and Menominee rivers, Lake Michigan; Munuscong Lake, St. Mary's River; and the Black and Cuyahoga rivers, Lake Erie. Frequencies of external and liver tumors were determined for brown bullhead (Ictalurus nebulosus) from all locations except the Black River and for walleye (Stizostedion vitreum) from the Lake Michigan and St. Mary's River sites. Sediment samples were analyzed for metals, polychlorinated aromatics, and polynuclear aromatic hydrocarbons (PAH). Liver neoplasms occurred in brown bullhead from the Cuyahoga River and Munuscong Lake; brown bullhead captured from Munuscong Lake were older than those collected from the other locations. Brown bullhead from these same two rivers had elevated hepatosomatic indexes. No liver neoplasms were found in brown bullhead from the Fox and Menominee rivers, although polychlorinated aromatics were highest in both Fox River sediment and Fox and Menominee brown bullhead, and arsenic was highest in Menominee River sediment and fish. Liver neoplasms in brown bullhead from the Cuyahoga River fit the prevailing hypothesis that elevated PAH in sediment can induce cancer in wild fish. The cause of the liver neoplasms in Munuscong Lake brown bullhead is undetermined.