As part of a larger investigation, northern pike (n = 158; Esox lucius) were collected from ten sites in the Yukon River Basin (YRB), Alaska, to document biomarkers and their correlations with organochlorine pesticide (total p,p'-DDT, total chlordane, dieldrin, and toxaphene), total polychlorinated biphenyls (PCBs), and elemental contaminant (arsenic, cadmium, copper, lead, total mercury, selenium, and zinc) concentrations. A suite of biomarkers including somatic indices, hepatic 7-ethoxyresorufin O-deethylase (EROD) activity, vitellogenin concentrations, steroid hormone (17B- ustradiol and 16-kebtestosteront) concentrations, splenic macrophage aggregates (MAs), oocyte atresia, and other microscopic anomalies in various tissues were documented in YRB pike. Mean condition factor (0.50 to 0.68), hepatosomatic index (1.00% to 3.56%), and splenosomatic index (0.09% to 0.18%) were not anomalous at any site nor correlated with any contaminant concentration. Mean EROD activity (0.71 to 17.51 pmol/min/mg protein) was similar to basal activity levels previously measured in pike and was positively correlated with selenium concentrations (r = 0.88, P < 0.01). Vitellogenin concentrations in female (0.09 to 5.32 mg/mL) and male (0.01 mg/mL in male pike from multiple sites indicated exposure to estrogenic compounds. Mean steroid hormone concentrations and percent oocyte atresia were not anomalous in pike from any YRB site. Few site differences were significant for mean MA density (1.86 to 6.42 MA/mm2), size (812 to 1481 ??m2), and tissue occupied (MA-%; 0.24% to 0.75%). A linear regression between MA-% and total PCBs was significant, although PCB concentrations were generally low in YRB pike (???63 ng/g), and MA-% values in female pike (0.24% to 0.54%) were lower than in male pike (0.32% to 0.75%) at similar PCB concentrations. Greater numbers of MAs were found as zinc concentrations increased in YRB female pike, but it is unlikely that this is a causative relationship. Histological abnormalities observed in gill, liver, spleen, and kidney tissues were not likely a result of contaminant exposure but provide information on the general health of YRB pike. The most common histologic anomalies were parasitic infestations in various organs and developing nephrons and nephrocalcinosis in posterior kidney tissues. Overall, few biomarker responses in YRB pike were correlated with chemical contaminant concentrations, and YRB pike generally appeared to be healthy with no site having multiple anomalous biomarker responses. ?? 2007 Springer Science+Business Media, LLC.