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ABSTRACT Numerous anthropogenic factors can deplete calcium (Ca) from forest ecosystems. Because an adequate supply of Ca is needed to support fundamental biological functions, including cell membrane stability and stress response, the potential for Ca deficiency following the individual, cumulative, or potentially synergistic, influences of anthropogenic factors raises important questions concerning organism and ecosystem health. Past work has shown that one Ca-depleting factor (foliar acid mist exposure) reduces concentrations of biologically important membrane-associated Ca (mCa) from red spruce foliar cells, destabilizes these cells, and results in their increased susceptibility to the freezing injury responsible for red spruce decline in northeastern U.S. montane ecosystems. Data presented here indicate that these same disruptions can occur for other tree species and that soil-based Ca manipulation can also alter critical mCa pools. Considering the unique role Ca plays in the physiological response of cells to environmental change and stress, we hypothesize that depletion of biologically available Ca (e.g., mCa) could result in a scenario similar to recognized immune deficiency syndromes in animals. A hypothetical pathway through which anthropogenically induced Ca deficiencies could predispose plants, and possibly animals, to exaggerated injury following exposure to environmental stress is presented, and the potential implications of this scenario to ecosystem health are discussed.