Our understanding of the effect of metals (including ions and theircompounds) on the immune system continues to evolve. Observedeffects include immunosuppression, immune stimulation, hypersensitivity, and autoimmunity. Many metals show a paradoxicaldose-response pattern comprising stimulation of immune functionat low doses and suppression at higher doses, but global immunefunction is often preserved due to the redundancy and the reservecapacity of the immune system, and clinically relevant effects areuncommon. Clinically relevant hypersensitivity reactions due tometals are dominated by T cell-mediated allergic contact dermatitis, particularly in response to exposure to beryllium, cobalt,chromium, gold, mercury, and nickel. Immediate (type I) hypersensitivity reactions dominated by airways symptoms occurinfrequently, and then most often with platinum, but rarely withnickel or chromium. The induction of metal-induced autoimmunity, including the formation of immune-complex deposits, is welldocumented in humans, but the number of recognized cases isfew. Studies in rodents using mercury and gold have increased ourknowledge of the mechanisms of metal-induced autoimmunity. Ofspecial importance is the unraveling of genetic factors that regulate susceptibility to mercury-induced autoimmunity, includingthe uptake and retention of mercury, as well as the threshold metalconcentrations for eliciting autoimmunity. Recently mercury, lead,and cadmium have been shown to accelerate and/or exacerbateautoimmunity in autoimmune-prone animal models. The importance of metal exposure for inducing and/or accelerating autoimmunity in humans remains to be determined.