Elastin is the major protein of elastic fibers and is responsible for the elastic recoil. Elastic fibers are a major component of the extracellular matrix in the human lamina cribrosa and undergo marked changes in primary open-angle glaucoma. Ultrastructural and immunocytochemical analysis demonstrated fragmentation of elastic fibers, accumulation of nonfibrillar elastic material, and bundles of microfibrils in the core of the cribriform plates in primary open-angle glaucoma. The changes in elastic fibers increased with the progression of the disease and strongly suggested abnormal biosynthesis, degradation of elastic fibers, or both. In this study, we used in situ hybridization and reverse transcriptase-polymerase chain reaction to localize and detect expression of elastin messenger RNA (mRNA) in human optic nerve heads with primary open-angle glaucoma and age-matched normal controls. The major finding of this study is the demonstration of elastin mRNA in the lamina cribrosa cells of optic nerve heads with primary open-angle glaucoma and the absence of this message in normal donors. Several studies have demonstrated a concordance between levels of elastin and relative levels of elastin mRNA. Our findings indicate de novo synthesis of elastin in the compressed lamina cribrosa in primary open-angle glaucoma. Synthesis of abnormal elastic fibers must alter the mechanical properties of the lamina cribrosa and may lead to compression, remodeling, and rearrangement of the cribriform plates characteristic of glaucomatous cupping.