The labile iron pool of cells (LIP) constitutes the primary source of metabolic and catalytically reactive iron in the cytosol. We studied LIP homeostasis in K562 cells using the fluorescent metal-sensitive probe calcein. Following brief exposure to iron(II) salts or to oxidative or reductive stress, LIP rose by up to 120% relative to the normal level of 350nM. However, the rate of recovery to normal LIP level differed markedly with each treatment (respective t1/2s of 27, 65-88 and < or = 17 min). We show that the capacity of K562 cells to adjust LIP levels is highly dependent on the origin of the LIP increase and on the pre-existing cellular iron status.