Using light microscopic immunohistochemistry, we studied the immunolocalization and immunoreactivity of the extracellular matrix, including collagen types III, IV, VI, laminin, and alpha elastin in the lamina cribrosa of monkey eyes with normal and experimentally chronic glaucoma. Our results showed: (1) abnormal linearlike immunodeposits of both collagen type IV and laminin in the margin of the lamina cribrosa with significant density in the glaucomatous eyes; (2) the immunoreactivity of collagen type III resembled that of the normal eye, but was slightly stronger at the laminar surface; (3) findings with collagen type VI resembled those of type III with an enhanced linearlike staining surrounding the nerve-fiber bundles. Furthermore, staining of alpha elastin demonstrated dramatic changes in both reactivity and localization. The lamina cribrosa of glaucomatous eyes showed a markedly reduced immunoreactivity as well as an irregular, interrupted pattern. These observations suggest that the changes might be a secondary to the long-standing elevation of intraocular pressure. The alteration of these macromolecules may modify the course of glaucomatous optic damage.