Soils and sediments downstream of Midland, Michigan, USA have elevated polychlorinated dibenzofuran (PCDF) and polychlorinated dibenzo-p-dioxin (PCDD) concentrations. To determine if the PCDD/DF concentrations have the potential to adversely affect terrestrial avian predators, a site-specific, multiple lines of evidence risk assessment was conducted for the great horned owl (Bubo virginianus; GHO). As long-lived resident top predators, the GHO has the potential to be exposed to relatively great concentrations of bioaccumulative compounds such as PCDD/DF. From 2005 to 2008, concentrations of PCDD/DF were measured in blood plasma of adult and nestling GHOs and addled eggs. Indicators of the condition of the population, including abundance and reproductive success, were collected along 115 km of river corridor. Fifty-five active 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) equivalents (TEQ(WHO-Avian)) nests were monitored in 21 breeding territories from 2005 to 2008. The geometric mean concentration in blood plasma of GHOs was greater in the study area (SA) than in the reference area (RA) for both adults (RA: 3.1; SA: 9.4 ng TEQ(WHO-Avian)/kg) and nestlings (RA: 0.82 ng TEQ(WHO-Avian)/kg, SA: 2.1 ng TEQ(WHO-Avian)/kg) GHOs, but less than concentrations expected to cause adverse effects based on laboratory studies. Concentrations of TEQ(WHO-Avian) in addled GHO eggs were also greater in the SA than the RA (50 and 7.3 ng/kg, wet weight, respectively), but were less than concentrations expected to cause adverse effects. The GHO population condition and productivity were both greater in the study area than in the reference area and were similar to other GHO populations. This result suggests the GHO population in the Tittabawassee River floodplain is consistent with what would be expected for this area.