The present study determined the effects of osmotic stress induced by sorbitol and KCl on apoptosis, Sorbitol induced apoptosis, activated the mitogen-activated protein kinase (MAPK) family and stimulated accumulation of cytosolic cytochrome c and procaspase-3 cleavage, KCl (0.2 M) also activated the MAPKs and induced cytosolic cytochrome c accumulation but did not induce procaspase-3 cleavage or apoptosis and was protective against sorbitol-induced apoptosis, However, when cells were exposed to KCI for 1 h, washed and returned to isotonic medium, caspase-3 was rapidly cleaved and apoptosis induced, We conclude that hyperosmotic KCl initiates early events in apoptosis but blocks caspase-3 activation by preventing the loss of intracellular K+, (C) 1998 Federation of European Biochemical Societies.