Environmental pollutants may affect the immune system of marine mammals in many areas of the industrialized world. This study provides the first evidence for metal-induced hypersensitivity in harbor seals and demonstrates a relationship between this immunopathy and the level of metals in blood. The concentrations of 20 essential and nonessential elements were analyzed in the blood of 13 harbor seals from the North Sea. In addition, their T-lymphocyte response to metals in terms of hypersensitivity was investigated using a lymphocyte transformation test (LTT) according to the MELISA (memory lymphocyte immunostimulation assay) modification. The results showed metal hypersensitivities in 7 of 11 seals investigated in MELISA (data from two seals could not be assessed), reflecting a positive or possible positive reaction in 13 of 154 total single tests. Four animals responded to one metal and three animals to multiple metals. The sensitizing metals were molybdenum (Mo), titanium (Ti), nickel (Ni), chromium (Cr), aluminum (Al), lead (Pb), and tin (Sn). Furthermore, the seals with a Ni-, Al-, and Cr-sensibilization showed the highest concentrations of these metals in blood. In 8 of the 13 positive cases, elevated blood metal concentrations correlated with the hypersensitivity reaction. Summarizing, we demonstrate in this first pilot study the potential immunological impact of metals in seals, a topic rarely investigated previously. Our results show the value of a combined biological and effect-monitoring tool to investigate pollution-induced immunopathies in live animals.