The aim of this study was to show that Cl−dependent excitotoxicity, with its characteristic cell swelling, involves actual water influx into the intracellular compartment. Taking advantage of the Ca2+omission paradigm of Cl−-dependent excitotoxicity, in the chick embryonic neural retinaex vivo, which is associated with toxicity levels (lactate dehydrogenase (LDH) release) considerably higher than those seen after simple exposure of the retinas to glutamate agonists, we have demonstrated that an intracellular water intake of 4.2 μl into retinal cells is associated with 13.3% total retinal LDH release. The fact that mannitol blocks both water inflow and LDH release appears to link both events from a pathogenic point of view.