Optic nerve heads from three premature infants and six adults were studied immunohistochemically to compare the extracellular proteins in the lamina cribrosa of young and old human eyes. In both age groups, antibodies to the basement membrane components laminin and collagen type IV were associated with blood vessels and laminar beam margins. In the adult eyes, interstitial collagen types I and III were heavily distributed within the laminar beams. Antibodies to fibrillin, the microfibrillar portion of elastin, labeled discrete, heavy bands oriented longitudinally within these beams. The beams of the neonatal lamina cribrosa contained much less interstitial collagen, with a predominance of collagen type III. Neonatal elastic tissue bands were less numerous and distinct within the laminar beams. These biochemical differences between the young and old lamina cribrosa may, in part, explain different clinical behaviors of the optic nerve head in congenital and adult glaucoma.