Sandhoff's disease (GM2 gangliosidosis type 2) was diagnosed in an infant in whom a progressive neurologic disorder and cherry-red foveal spots developed. At autopsy, ultrastructural examination of the retina and optic nerve disclosed abundant pleomorphic storage cytosomes in all neurons of the retina, including the inner segments of the photoreceptor cells, and in glial cells of the optic nerve. Electron microscopy of the cornea showed, within the keratocytes, distended clear lysosomes that contained some fibrillogranular material and an occasional collection of lamellae. We discuss the pathogenesis of the clinical and pathologic ocular findings with regard to the inherited absence of the enzymes hexosaminidase A and B and an accumulation of the substrates, GM2 ganglioside and asialo GM2, in the nervous system (including retina and optic nerve) and globoside and other hexosamine-containing substances in the viscera (including cornea).