The application of unlabelled glutamate to the isolated chicken retina charged with [14C]glutamate caused an increase in the tissue transparency and a release of the label into the superfusion fluid. The processes causing the change in transparency were 'desensitized' by a prolonged application of unlabelled glutamate, whereas the release of the labelled amino acid was relatively unaffected. Mgz+ tended to depress the change in transparency caused by stimulation with unlabelled glutamate but had little effect on the release of labelled glutamate from the retina. The effect of a Caz+-free superfusion fluid on the transparency and release of glutamate varied from retina to retina. Aspartate (in higher concentrations) elicited a change in transparency and release of the label in a manner similar to that of glutamate. Glutamine caused a change in transparency accompanied by a release of labelled glutamine and in some experiments the release of a small amount of labelled glutamate. Homocysteic acid elicited marked changes in transparency but no release of labelled glutamate. Pyroglutamate depressed both the change in transparency and the release of labelled glutamate caused by the unlabelled amino acid. Gamma-aminobutyric acid and glycine had no effect on the transparency of the tissue or on the release of amino acids. We have discussed the possibility that a release of glutamate from the intracellular compartment into the extracellular space is involved in the mechanism of spreading depression.