Background: Systemic cyclosporine can produce gingival overgrowth, but conjunctival reactions have not been reported. Purpose: The purpose of this study is to report the clinical and histopathological findings of a case of bilateral enlargement of the plica semilunaris associated with oral cyclosporine. Methods: A renal transplant recipient developed hypertrophy of both plicae semilunares after 18 months of oral cyclosporine. The conjunctival specimens were processed for light microscopic examination and immunohistochemical analysis. Results: Histopathologic findings included numerous plasma and plasmacytoid cells containing IgG crystals. Conclusion: Oral cyclosporine may cause enlargement and plasma-cell infiltration of the plica semilunaris, possibly by affecting cellular immunity and cytokine production in the irritated conjunctival mucosa.