On the basis of experiments with primary cultures of mouse astrocytes with conventional K+-sensitive intracellular microelectrodes involving ''chemical ischemia'' (antimycin a and sodium fluoride treatment), a model of ischemia is presented. According to this model, ischemia has no significant direct effect during the first 10 min on astrocytes; neurones, however, lose a major part of their K+ into the ECS. This leads to an astrocytic depolarization, which in turn activates astrocytic anion channels. This will result in passive, Donnan-mediated K+, CI– and HCO3̄ fluxes into astrocytes, which in turn causes swelling and a collapse of the ECS. Arguments are put forward that this may explain the swelling of astrocytic endfeet, which occurs very early in an ischemic insult.