Mooren's ulcer is a chronic, painful rodent nonpurulent corneal ulcer. In order to discern the possible role that immunological processes (antibody and cell-mediated) play in the development of a Mooren's ulcer, we evaluated sera from patients (n = 16) for the presence of circulating antibodies against normal rabbit and human corneal epithelium using an indirect immunofluorescent technique (IFT) and determined the T-lymphocyte subsets (CD4, CD8, CD11) in the peripheral blood. This condition was treated with an immunophilin, cyclosporin A (CsA) (0.5% solution), applied topically. Antibodies against rabbit corneal epithelium were detected in 12 of 16 patients (75%), while only six of 16 (37.5%) patients had antibodies against human corneal epithelium. The percentage of CD8 (suppressor T cells) T lymphocytes was significantly lower in patients with Mooren's ulcer than in the controls (p < 0.01). Mooren's ulcer was effectively treated with 0.5% CsA in 11 of 18 (61.1%) affected eyes (n = 14 patients), as determined by long-term (24-31 months) follow-up. We noted particularly that regulatory imbalance existed in the immune systems of the patients. We also think that the limbus and conjunctival lymphoid tissue adjacent to the limbus might play an important role in the pathogenesis of the disease. The detection of serum antibodies against corneal epithelium and determination of T-lymphocyte subsets in the peripheral blood may provide a referential basis for the clinical diagnosis of Mooren's ulcer. Effective treatment with 0.5% topical CsA is primarily through the depression of ocular immunoreactions, although systemic action is not completely ruled out.