Polybrominated diphenyl ethers (PBDEs) are persistent, bioaccumulative, organohalogen compounds that are increasing exponentially in the Great Lakes (Canada/USA) biota. The present study was undertaken to examine the immunological effects of a commercial PBDE mixture in ranch mink (Mustela vison). Twenty-week-old mink (n = 10 mink/group) were exposed to 0, 1, 5, or 10 ppm of DE-71 through their diet for eight weeks. The phytohemagglutinin-induced cutaneous reaction, and antibodies specific to keyhole limpet hemocyanin conjugated to dinitrophenol were measured. Liver microsomal ethoxyresorufin-O-deethylase (EROD) activity also was measured. Organs were weighed and spleens were examined histologically. No differences were found in the PHA-induced skin response in exposed mink; mink in the two highest treatments exhibited significant increases in antibody production over control mink. Systemic toxicity was apparent; significant body weight reductions were found in mink exposed to 5 and 10 ppm of DE-71. Exposed mink had significantly larger relative spleen, adrenal, and liver masses than control mink. Spleens of mink exposed to 10 ppm of DE-71 had significantly increased germinal center development and incidence of B-cell hyperplasia. The activity of EROD was induced in all treated mink relative to controls and was positively associated with the liver somatic index. Hematocrit in mink from the two highest exposure groups was significantly lower than control mink. Percentage neutrophils increased and percentage lymphocytes decreased significantly in mink from the higher two dosage groups. Our findings have direct relevance to wild mink in the Great Lakes ecosystem, because mink are top predators of the aquatic food web, providing evidence for the vulnerability of this species to the effects of environmental PBDE mixtures.