This study was undertaken to investigate the role of afferent spontaneous electrical activity in regulating death of target cells in the developing mammalian visual system. We show here that naturally occurring cell death in the rat superior colliculus is greatly augmented when the spontaneous firing of retinal ganglion cells is transiently blocked with TTX. An increased number of dying cells is already observed after 1 hr of afferent blockade. A 50% increase of cell death is reached after 3 hr of blockade, an effect that closely parallels increased cell death caused by eye enucleation after similar intervals of time. These results suggest that, during development, input cells exert a trophic action on target cells, which is prevented by silencing input electrical activity. A likely explanation of this effect is that the spontaneous firing of input cells causes the release by afferent fibers of a trophic agent promoting the survival of target cells.