Antibodies were prepared against large ganglion cells isolated from bovine retina and injected into the vitreous chamber of 1 eye in 6 adult cats. The other eye of each cat received either a control pre-immune gamma-globulin injection or was untreated. After a survival time of 9-86 days, ganglion cell density was assessed from Nissl-stained retinal whole-mounts. In each cat, there were fewer large ganglion cells (alpha-cells) in the immunoglobulin-injected retina than in the control retina. The reduction in large ganglion cells occurred in patches adjacent to areas of approximately normal large ganglion cell density. Counts of the number of large ganglion cells in both eyes of the 6 cats indicated that the immunoglobulin injected eyes had from 8% to 61% (mean 32%) fewer large ganglion cells than the paired control eyes. This was significantly greater than the difference in the number of large ganglion cells between pairs of normal or control-injected eyes. The magnitude of the effect was not related to the survival time following the immunoglobulin injection. Cell size measures of all ganglion cells in selected areas of retina indicated that the small ganglion cells were unaffected by the antibodies. However, there was a suggestion that the largest of the medium size ganglion cells were affected in addition to the large ganglion cells. Counts of total ganglion cells per unit area in affected regions of retina revealed a reduced overall density, suggesting that the ganglion cells were lost rather than decreased in size. These results indicate that antibodies to the large ganglion cells can be used to reduce the number of large ganglion cells (alpha-cells) in the cat retina. Since these cells correspond to the Y-cell functional class of ganglion cells in the cat retina, the antibodies may provide a useful tool for studying Y-cell function in the visual pathways.