Associations between contaminant exposure and liver and skin tumor prevalence were evaluated in brown bullheads (Ameiurus nebulosus) from the tidal Potomac River watershed. Thirty bullheads (>260 mm) were collected from (1) Quantico embayment, near a Superfund site which released organochlorine contaminants; (2) Neabsco Creek, a tributary with petroleum inputs from runoff and marinas; and (3) Anacostia River (spring and fall), an urban tributary designated as a Chesapeake Bay Region of Concern, contaminated with PCBs, PAHs, and organochlorine pesticides. Fish were collected from the Tuckahoe River, as a reference. Cytochrome P450 activity, bile PAH metabolites, and muscle organochlorine pesticide/PCB concentrations were measured in randomly-selected individuals and sediment contaminants were analyzed. We found statistically significant differences in liver tumor prevalences: Anacostia (spring)-50%, Anacostia (fall)-60%, Neabsco-17%, Quantico-7%, Tuckahoe-10%. Skin tumor prevalences were significantly different: Anacostia (spring)-37%, Anacostia (fall)-10%, Neabsco-3%, Quantico-3%, Tuckahoe-0%. Tumor prevalence in Anacostia bullheads warrants concern and was similar to those at highly contaminated sites in the Great Lakes. There was evidence of higher PAH exposure in Anacostia fish but a cause-effect linkage cannot be established. Fish tumor surveys, with histopathological examination of internal and external organs, are recommended for monitoring the status of Regions of Concern.