Experimental literature suggests that polychlorinated biphenyls (PCBs) alter thyroid function however studies of non-occupational or acute exposures in human populations have presented equivocal results. This study considered associations between PCBs and thyroid function biomarkers in a specially selected subsample of participants from the New York State Angler Cohort Study, with the goal of hypotheses generation. Between 1995 and 1997, 38 subjects donated a blood specimen and completed a questionnaire. Sera were analyzed for 77 PCB congeners, beta-HCH, DDE, HCB, mirex, oxychlordane, and trans-nonachlor using GC-ECD, as well as for lipids components, thyroid stimulating hormone (TSH) and free thyroxine (FT(4)). A priori, the sum of all 77 measured PCB congeners, 27 individual PCB congeners with literature evidence for thyroid effects, their sum, DDE, and HCB were chosen as potential predictors for thyroid function. Age, body mass index, cigarette smoking, gender, and use of thyroid relevant medications were considered as important covariates. Adjusted for log total serum lipids, significant (P<0.05) bivariate correlations were demonstrated for log PCB IUPAC #s 153 (r=0.33), 170 (r=0.38), 171+156 (r=0.36), and 180 (r=0.35) with FT(4); however none were observed for log TSH. Using a forward stepwise selection procedure and confounder evaluation algorithm, log PCB #170 was a significant positive predictor of serum FT(4) (beta=1.55 95%CI 0.04-3.07), adjusted for mean centered log PCB #187 and log serum total lipids. This association may be explained by competitive binding to serum thyroid binding proteins by PCB #170, its hydroxylated metabolite 4'-OH-PCB172, or other related but unconsidered compounds. However, bias due to the use of a competitive analog assay for free hormone measurement, random error, or uncontrolled confounding cannot be excluded. The results of this study suggest that Lake Ontario sportfish consumers may comprise a high risk population for PCB related thyroid function alteration and warrant a larger confirmatory investigation.