Brown bullheads (Ameiurus nebulosus) were collected from 2 locations near Baltimore, Maryland, Back River and Furnace Creek, and 1 (reference) location, Tuckahoe River, to compare the prevalence of tumors (liver and skin) and visible skin lesions (fin erosion and abnormal barbels). Cytochrome P450 activity measured as ethoxyresorufin-O-deethylase, biliary PAH-like fluorescent metabolites, and fillet contaminant concentrations were determined as indicators of exposure in a randomly selected subset of the fish. There were no significant differences in liver tumor prevalence: Back River = 8% (4/50), Furnace Creek = 0% (0/50), and Tuckahoe River = 2.6% (1/39; p = 0.20, extension of Fisher’s exact test). Skin tumor prevalence was as follows: Furnace Creek = 12% (6/50), Back River = 8% (4/50), and Tuckahoe River = 0% (0/39; p = 0.063). In the Back River fish, there was a 40% (20/50) prevalence of fin erosion and a 28% (14/50) prevalence of abnormal (shortened, clubbed, or missing) barbels. Fin erosion was not observed in the other collections, and only 10% (5/50) of the Furnace Creek fish had abnormal barbels (p < 0.001 for both lesions). There were statistically significant differences in mean EROD activity, with levels in Furnace Creek and Back River fish approximately twice that found in Tuckahoe River fish. There were also significant differences in mean benzo(a)pyrene-like bile metabolite concentrations: the lowest mean was in the Tuckahoe River fish, 8 times higher in Furnace Creek fish, and 13 times higher in Back River fish. Of the 3 groups, the Back River bullheads appear to be most adversely affected by contaminant exposure because they had the highest prevalence of liver tumors, fin erosion, and abnormal barbels.