PURPOSE: The overproduction of immunoglobulin E (IgE) antibodies is associated with vernal keratoconjunctivitis (VKC). CD23/CD21 and CD40/CD40 ligand (CD40L) interactions have been proposed to be involved in the regulation of IgE synthesis. The purpose of the present study was to investigate the presence and distribution of CD23, CD21, CD40 and CD40L in the conjunctiva from patients with active VKC. METHODS: Conjunctival biopsy specimens from 8 subjects with active VKC and 6 control subjects were studied. We used immunohistochemical techniques and a panel of monoclonal antibodies (mAbs) directed against CD23, CD21, CD40 and CD40L. In addition, a panel of mAbs were used to characterise the composition of the inflammatory infiltrate. RESULTS: In the normal conjunctiva, basal epithelial cells and vascular endothelial cells in the upper substantia propria showed a constitutive very weak immunoreactivity for CD40. The immunoreactivity for CD23, CD21 and CD40L was absent. In VKC specimens, the stromal inflammatory infiltrate was orgnanised as a diffuse infiltrate and as small lymphoid follicles consisting of CD20+ B lymphocytes intermingled with smaller numbers of CD3+ T lymphocytes, and CD68+ monocytes/macrophages. Lymphocytes in the centre of the lymphoid follicles showed CD23 and CD21 immunoreactivity. CD40 immunoreactivity in epithelial cells and vascular endothelial cells was stronger in VKC specimens than in control eyes. Furthermore, the majority of mononuclear cells, including T and B lymphocytes, showed immunoreactivity for CD40. CD40L immunoreactivity was not detected. CONCLUSION: B lymphocytes in the lymphoid follicles expressing CD23, CD21 and CD40 are activated and might be precursors of IgE-producing B cells. These results suggest that the conjunctiva might contribute to IgE synthesis.