In the retina, cell fate determination is thought to be regulated by a series of local cell-cell interactions. Evidence suggests that retinal precursors utilize Notch-mediated intercellular signaling to regulate their fates. However, the identity of the endogenous ligand and its role in the Notch-signaling pathway is not well understood. We have identified C-Delta-1 as the putative endogenous ligand for Notch, in the developing chick retina. C-Delta-1 is coexpressed spatially and temporally with C-Notch-1 and their expression is associated with the temporal aspects of cell birth in the developing retina. This suggests that Delta-Notch signaling is utilized to maintain progenitors in an uncommitted state and that a subtle fluctuation in this signaling helps to sort out competent cells during successive cell-fate determination. We have tested the latter possibility in the specification of the ganglion cells. In early stages of retinal development when ganglion cells are the predominant cells born, decreasing C-Delta-1 expression with antisense oligonucleotides increases the proportion of RA4 antigen-expressing ganglion cells which are recruited predominantly in the periphery. Conversely, use of exogenous Drosophila Delta leads to a decrease in the RA4 antigen-expressing ganglion cells. Our results suggest that C-Delta-1 activation of the Notch pathway regulates the specification of retinal neurons in general and of ganglion cells in particular.