Abstract: A method for reducing calcium overload in cells to prevent the transition from reversible to irreversible injury. The cell surface is treated with an organic polycation selected from the group consisting of protamine, dodecyltrimethylammonium bromide, polymyxin B sulfate and polybrene which is capable of altering the cells surface charge sufficiently to eliminate or reduce the influx of calcium resulting from exposure to noxious stimuli. The method may be used both in vivo and in vitro. The method is effective in preventing calcium uptake in a variety of cell injury situations including metabolic inhibition and free radical attack.