Experimental occlusion of the central retinal vessels in albino rats followed by reperfusion for 2 or 4 days resulted in a highly active proliferative response. Mitotic figures were produced in retinal vascular cells, presumed Müller cells, retinal pigment epithelial cells, and possibly other cell populations in the retina. A large number of mitoses were observed in 60-100% of 50 experimental eyes with 2, 4 or 6 hr of experimental ischemia and 2 or 4 days of reperfusion and in none of the 37 control eyes. Autoradiography demonstrated 3H-thymidine uptake in the retina and in vascular cells on a trypsin digest preparation of the retina. Retinal ischemia followed by reperfusion leads to mitosis of retinal cells. This suggests a causal relationship in proliferative retinopathies where ischemia and cell proliferation coincide.