Endocytosis is enhanced in some cases of neuronal death. We report for the first time that intraocular injections, in chick embryos, of excitotoxic doses of kainate induce strong endocytosis in retinal amacrine cells destined to die and that even subtoxic doses can induce some degree of endocytosis. That the uptake was due to endocytosis rather than passive diffusion through the plasma membrane was shown ultrastructurally. The endocytosis was demonstrated by using three unrelated tracers--horseradish peroxidase, microperoxidase, and 4.4-kDa fluorescein isothiocyanate (FITC)-labeled dextran--suggesting that it does not depend on the binding of the tracers to a particular receptor. However, it appears to be surprisingly sensitive to the size of the ligand, because a heavier (42-kDa) FITC-dextran was not endocytosed. The induction of endocytosis by kainate can occur even when protein synthesis is blocked. These results indicate that toxic or near-toxic doses of kainate induce endocytosis, raising the question of whether this is mechanistically implicated in causing or preventing excitotoxic neuronal death.