The accumulation of calcium during myocardial hypoxia or ischaemia followed by reoxygenation or reperfusion is related to the development of cell necrosis and may be an important causal mechanism. Influx of calcium is a late event during hypoxia but occurs abruptly on reoxygenation or reperfusion. On reoxygenation calcium influx is not altered by nifedipine or quiescence but can be prevented by nickel (3 mM), cyanide (5 mM) or FCCP (10(-6) M). The extracellular marker 51Cr-EDTA does not enter the intracellular fluid on reoxygenation but can when the cell membrane is disrupted by a detergent, Brij'35, or the calcium paradox. The results suggest that the uptake of calcium on reoxygenation or reperfusion is related to the reintroduction of oxygen and caused by an increased calcium influx down the concentration gradient. The flux is not through the slow calcium channel and is not due to disruption of the membrane. The effects of CN- and FCCP and the unaltered calcium efflux suggest that the major part of the calcium uptake is stored in intracellular compartments and is not located in the intracellular fluid.