Systemic lupus erythematosus (SLE) is an autoimmune disease occasionally involving the conjunctiva, sclera or cornea. The immunopathology of the active epibulbar lesions has not been studied in detail. Conjunctival biopsies from 11 SLE patients with active epibulbar lesions and from 12 age-matched individuals undergoing cataract surgery were analysed by light microscopy, immunofluorescence and immunoperoxidase techniques. SLE patients presented with scleritis (3 cases), peripheral ulcerative keratitis (5 cases) or progressive cicatrising conjunctivitis (5 cases). Histologically, SLE specimens showed moderate subepithelial and perivascular mononuclear cell infiltration or granuloma formation in the substantia propria, and squamous metaplasia; thrombosis was not seen. Immunoreactant deposition was present at the epithelial basement membrane in 4 of 5 cases with cicatrising conjunctivitis. Vascular immunodeposits wer detected in 4 cases. The epithelium showed increased T helper cells (CD4+), granulocytes and natural killer cells (CD67+), dendritic cells (CD1+), and an increase in HLA-DR expression compared with normal tissue. In the substantia propria, B cells (CD22+), macrophages (CD14+), dendritic cells, activated T cells (CD25+, CD3+), the T helper (CD4+)/T suppressor (CD8+) ratio and HLA-DR expression were all increased. These observations suggest that the rare epibulbar manifestations in SLE result from immune-complex-mediated reactions.