In this study we have shown that redistribution of the lipid composition of the external and internal leaflets of the PM during apoptosis results in two main alterations in the cell surface, externalisation of PS, and a looser packing of the lipid hydrophobic head groups in the external leaflet. Significantly, neither of these alterations can be directly implicated in the mechanism of apoptotic cell shrinkage, however they do have functions in other phases of the apoptotic process. Progressional studies involving morphological and flow cytometric evaluation, and DNA gel electrophoresis revealed that apoptotic cell shrinkage is associated with a decrease in [Na+]i and [K+]i which occurs after visualisation of chromatin condensation and internucleosomal DNA fragmentation, and prior to apoptotic body formation. When apoptotic cultures were supplemented with inhibitors of the Na+, K+-ATPase pump or the Ca2+-dependent K+ channel, essentially all of the respective Na+ or K+ efflux during apoptosis can be inhibited, suggesting that essentially all of the Na+ and K+ efflux can be ascribed to active pumping via the Na+, K+-ATPase pump and the Ca2+-dependent K+ channel.