Increased pinniped and dolphin mortality rates have led to speculations that persistent pollutants, in particular polychlorinated biphenyls (PCB), are immunomodulatory, making individuals susceptible to infections. The aim of the present study was to investigate effects that PCB may exert on peripheral blood mitogen-induced lymphocyte proliferation responses in free-ranging gray seal (Halichoerus grypus) pups from the polluted Baltic Sea and from the cleaner open waters of the Atlantic Ocean. T-cell mitogen (phytohemagglutinin [PHA] and concanavalin A [Con A]) and T-/B-cell mitogen (pokeweed mitogen [PWM]) responses were significantly lower in the more PCB-contaminated Baltic gray seal pups than in reference pups from the Atlantic. Best regression analysis revealed that dioxin-like mono-ortho PCB accounted for the immunosuppressive responses. In the Baltic seals, the immunosuppressive effects were limited to the more persistent dioxin-like mono-ortho PCB. In the Atlantic seals a positive correlation existed between PCB concentrations and mitogen-induced lymphocyte proliferation responses. Although direct cause-effect relationships are difficult to demonstrate in free-ranging animals, our results are consistent with the weight of evidence available that PCB, and dioxin-like PCB in particular, modulate lymphocyte function in free-ranging marine mammals. Thus, exposure to PCB most likely result in increased susceptibility to infections or reduced host resistance in pinnipeds.