Adult walleye were collected from several locations in the Lower Fox River and Green Bay, Wisconsin (the assessment area) and two relatively uncontaminated reference locations (Lake Winnebago and Patten Lake, Wisconsin) between July and October in 1996 and 1997. Whole body and liver samples collected in 1996 were analyzed for total PCBs, PCB congeners, and liver histological lesions. Follow-up sampling in 1997 included examination of liver histopathology, PCBs in liver samples, measurement of ethoxyresorufin-O-deethylase (EROD) activity, immunological evaluation of kidney and blood samples, measurement of plasma vitellogenin, and examination of tissues for parasites as well as bacterial and viral infections. Mean PCB concentrations in whole body and liver samples were elevated in assessment area walleye (4.6 to 8.6 and 3.6 to 6.4 mg/kg wet weight, respectively) compared to PCB concentrations in reference areas (0.04 mg/kg in walleye fillets from Lake Winnebago). A significant (p < 0.01) elevation was observed in the prevalence (26%) of hepatic preneoplastic foci of cellular alteration (FCA) and neoplasms in 5 to 8 year old walleye collected from the assessment area, compared to reference area fish (6% prevalence). Walleye from the assessment area also contained multiple FCA and hepatic tumors per liver sample, whereas no tumors and a reduced prevalence of FCA were observed in reference area walleye. Both tumors and FCA were more prevalent in female fish than in male fish within the 5 to 8 year age classes. There were no remarkable effects on immunological parameters in assessment area walleye, although hematocrit was elevated and blood monocyte counts were 40% lower than those of reference area fish. The data did not show any clear distinctions in the prevalence of disease between reference and assessment area walleye. EROD activity was similar in assessment area and reference area walleye. Plasma vitellogenin was elevated in female walleye from eastern Green Bay, but was not detected in male fish from this location. The results of this investigation demonstrate significant elevation in hepatic preneoplastic lesions and hepatocellular adenomas and carcinomas in assessment area walleye exposed to elevated concentrations of PCBs. These histopathological lesions are consistent with long-term exposure to tumor promoters such as PCBs, although quantitative association between tumors and PCBs was not observed at the level of the individual fish. Additional research would be needed to elucidate the causal mechanisms underlying tumorigenesis.