Hexachlorobenzene (HCB) is a persistent substance that accumulates in tissues and biomagnifies up the food chain suggesting that biota at higher trophic levels (e.g., predatory birds and piscivorous mammals) are at the greatest risk of exposure. Although widespread, the highest levels of HCB in Canada are found in the Great Lakes and connecting channels. Because mink (Mustela vison) are piscivorous mammals known to be particularly sensitive to the effects of organochlorine substances, we assessed whether mink populations in the Great Lakes area are experiencing adverse effects as a result of exposure to HCB. A deterministic, deliberately hyperconservative analysis indicated that recent levels of HCB in air, water, and aquatic organisms are unlikely to pose a significant risk to mink living near Lakes St. Clair, Erie and Superior. The hazard quotients for the St. Clair River area near Sarnia and Lake Ontario, however, indicated potential risks. We conducted Monte Carlo simulations to estimate the probability that mink exposed to HCB in these areas are experiencing reproductive impairment. The results of these analyses indicate: (1) a moderate to high probability that mink in the St. Clair River area are experiencing 5 to 20% declines in reproductive success due to HCB exposure, and (2) a low probability (<15%) that mink near Lake Ontario are experiencing even modest declines in reproductive fecundity (>5%).