St. Lawrence Island, Alaska, is the largest island in the Bering Sea, located 60 km from Siberia. The island is home to approximately 1600 St. Lawrence Island Yupik residents who live a subsistence way of life. Two formerly used defense sites (FUDS) exist on the island, one of which, Northeast Cape, has been the subject of a $123 million cleanup effort. Environmental monitoring demonstrates localized soil and watershed contamination with polychlorinated biphenyls (PCB), organochlorine (OC) pesticides, mercury, and arsenic. This study examined whether the Northeast Cape FUDS is a source of exposure to OC pesticides. In total, 71 serum samples were collected during site remediation from volunteers who represented three geographic regions of the island. In addition, ninespine stickleback (Pungitius pungitius) and Alaska blackfish (Dallia pectoralis) were collected from Northeast Cape after remediation to assess continuing presence of OC pesticides. Chlordane compounds, DDT compounds, mirex, and hexachlorobenzene (HCB) were the most prevalent and present at the highest concentrations in both fish tissues and human serum samples. After controlling for age and gender, activities near the Northeast Cape FUDS were associated with an increase in serum HCB as compared to residents of the farthest village from the site. Positive but nonsignificant relationships for sum-chlordane and sum-DDT were also found. Organochlorine concentrations in fish samples did not show clear geographic trends, but appear elevated compared to other sites in Alaska. Taken together, data suggest that contamination of the local environment at the Northeast Cape FUDS may increase exposure to select persistent OC pesticides.