In the absence of appropriate stimulus, eosinophils in vitro rapidly exhibit the features of apoptotic cells (nuclear pycnosis, cell shrinkage, DNA fragmentation). By using electronic cell sizing, we precisely measured the volume distribution of human eosinophils during apoptosis. We observed that apoptosis of eosinophils was accompanied by a marked cell volume decrease (approximately 60%). Moreover, analysis of the volume distribution in different experimental conditions (kinetics of apoptosis, inhibition of apoptosis by cytokines) revealed that the cell shrinkage, once triggered, was a fast process in which the intermediate states between normal and shrunken volume had a short half-life. As a model of apoptosis, the eosinophil model allowed us to test the hypothesis that apoptotic cell shrinkage was linked to osmotic changes due to leakage of internal ions. Indeed, in the presence of K+ channel blockers, the shrinkage was inhibited in a dose-dependent manner. In conclusion, our results suggest that eosinophil shrinkage during apoptosis is a striking and rapid phenomenon and osmotic changes due to K+ efflux could be responsible, at least in part, of the volume decrease.