Double-antibody immunofluorescent studies of sectioned human optic nerve head indicated the marked presence of collagen type IV and laminin in the extracellular matrix of the lamina cribrosa. These macromolecules were layered transversely across the nerve fascicles and appeared to constitute the cribriform plates. Relatively little collagen types III and I were present in the extracellular matrix of this tissue and fibronectin was not detected in appreciable amounts. These results indicated that the lamina cribrosa contains a specialized extracellular matrix of the central nervous system made up of plates of material resembling basement membrane. The major macromolecular components of the lamina cribrosa do not resemble those of sclera.