There is an exchangeable calcium pool in both normal and sickle cell erythrocytes, comprising about 10-15% of the total cellular calcium. Sickle cells show increased calcium as compared to normal cells in the oxygenated state. Specific differences between sickle and normal cells which may be associated with this fact are an increased rate of calcium exchange in sickle cells at low external calcium, an increased "leak" of calcium into sickle cells (i.e., phosphate independent exchange), and a pattern of magnesium loss in sickle cells which is consistent with a Mg-Ca exchange diffusion resulting in the increased intracellular calcium in these cells. The exchangeable calcium in sickle cells is more labile, almost all of it being available for re-exchange out of the cell over a short-time-course experiment. Analyses of flexibility and osmotic fragility of sickle cells are consistent with expected effects of increased intracellular calcium.