Systemic administration of monosodium-l-glutamate by single injections of 4 mg/g body weight in infant rats (2-10 days of age) results in acute swelling of cytoplasm and nuclear pyknosis of neurons in the stratum zonale and stratum griseum superficiale of the superior colliculus. Multiple daily doses of 4 mg/g body weight monosodium-l-glutamate result in an almost complete loss of neurons in these two superficial layers. The deeper layers appear not to be affected. No pathological effects were observed in the lateral geniculate body or pretectal complex. Light- and electron-microscopic studies reveal that the optic nerves are remarkably shrunken and many myelinated as well as unmyelinated axons are lost. Injection of 3H-proline into the vitreous body of one eye results in limited transport to the suprachiasmatic nucleus, lateral geniculate body and to lateral portions of the superior colliculus. The small percentage of intact axons in the optic nerve, as well as the limited proline transport from the eye, suggest that administration of monosodium-l-glutamate leaves intact some optic fibers, a portion of which belongs to the retinohypothalamic tract.