We have studied the effect of ischemia on the cellular distribution of glutathione in the rat retina using immunocytochemical methods. Distinct degrees of ischemia were induced by varying the length of the post-mortem interval until fixation of the retina. In immediately fixed retinas, glutathione was confined exclusively to retinal Müller cells. In retinas fixed 5-10 min post-mortem, glutathione levels in Müller cells were reduced concomitant with incipient labeling in retinal neurons. Post-mortem intervals longer than 10 min resulted in strong labeling of neurons, particularly of retinal ganglion cells, whereas Müller cells were essentially devoid of immunoreactivity. Our data suggest transfer of glutathione from glia cells to neurons under ischemic conditions. Such a mechanism, utilizing the antioxidant properties of glutathione could be part of a glia-neuronal interaction contributing to the amelioration of oxidative stress and explain the high tolerance of the rat retina against ischemia/reperfusion injury.