We employed the novel technique of infrared videomicroscopy to study the morphological changes induced by the neurotoxicity of high concentrations of L-glutamate and by anoxia. The infrared videomicroscopy system described uses an inverted microscope and employs a combination of infrared illumination, differential interference contrast (DIC) and contrast enhancement by video. With this system, we were able to observe swelling of neurons 50 microns deep in rat neocortical slices after bath application of glutamatergic agonists or during anoxia. By recording in time lapse mode it was possible to visualize the dynamics of cell swelling and to demonstrate neuroprotection by glutamatergic antagonists. The method may be of use in screening of potential neuroprotective drugs for stroke therapy.