Dietary exposures of great horned owls (GHO; Bubo virginianus) to polychlorinated biphenyls (PCBs) in the terrestrial food web at the Kalamazoo River, Michigan, USA, were examined. Average potential daily doses (APDD) in GHO diets were 7- to 10-fold and 3-fold greater at the more contaminated location versus a reference location for site-specific exposures quantified as total PCBs and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ_WHO-Avian), respectively. Wetland/aquatic prey contributed significantly to PCB exposure and APDD. Estimates of risk based on comparison of modeled dietary intake (e.g., APDD) to toxicity reference values (TRVs), using a hazard quotient (HQ) methodology, varied between diet composition methods (mass basis vs numeric basis). Mass-basis compositions yielded greater HQs at all sites. Potential risks associated with dietary exposures (“bottom-up” risk assessment methodology) were less than (HQ < 1) benchmarks for effects,. This result is consistent with risk estimates based on concentrations in tissues (“top-down” risk assessment methodology), and indicated PCBs posed no significant risk to terrestrial raptor species. Colocated and concurrent studies that evaluated GHO reproductive performance (nestling productivity) and relative abundance were consistent with results of the risk assessment. Measures of risk based on HQs were consistent with direct measures of ecologically relevant endpoints (reproductive fitness). Uncertainty in risk estimates is contributed during the selection of TRVs for effects in GHO based on TEQ_WHO-Avian because of the absence of species-specific, dose-response thresholds. This evaluation indicated that a multiple-lines-of-evidence approach provided the best estimate of risk.