The in situ immune reaction occurring in the conjunctival tissues of patients with vernal keratoconjunctivitis was studied using immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies. Our data point to a complex immunopathogenesis of the disease. The anaphylactic response was demonstrated by the presence of many eosinophils and mast cells showing membranous IgE staining in the epithelial and stromal inflammatory infiltrate. IgE+ plasma cells were rare or absent in the conjunctival tissues and around the acini of accessory lacrimal glands, suggesting that IgE is not produced locally in the conjunctival tissues. A humoral immune response was evidenced by the presence of small B-lymphoid follicles, scattered B-lymphocytes, and many plasma cells in the stromal inflammatory infiltrate. IgA+ and IgG+ plasma cells were of more or less equal numbers and outnumbered IgM+ plasma cells. The majority of plasma cells around the acini of accessory lacrimal glands were IgA+. A role played by cell-mediated immunity was evident from the presence of scattered stromal T-lymphocytes and many dendritic cells in the epithelium and stroma. Some stromal dendritic cells carried IgE on their surfaces.