BALB/c-derived athymic, nude (nu/nu) mice exhibited a heightened natural resistance to experimental corneal infection with Pseudomonas aeruginosa when compared with their heterozygote (nu/+) littermates. Stereomicroscopic examination of the eyes of nu/nu mice 24 h after corneal trauma and topical bacterial application revealed slightly cloudy corneas (iris visible), whereas nu/+ littermate corneas were opaque (iris not visible). Nu/+ mice failed to resolve the infection, and endophthalmitis and shrinkage of the infected eye occurred in these mice within 2 weeks after experimental Pseudomonas infection, as in the parent BALB/c strain. However, nu/nu mice, similarly infected, resolved the infection within 24 h and never exhibited full corneal opacity or eye shrinkage. Histological examination of the corneas of nu/nu mice 24 h after experimental wounding and bacterial application demonstrated subepithelial capillaries and a few polymorphonuclear neutrophils (with numerous intracellular bacteria) in the central cornea. In contrast, the equivalent corneal areas of infected nu/+ littermates, examined similarly, showed a more striking neutrophilic response (but with few intracellular bacteria) to similar bacterial infection, as well as a lack of blood vessels within the central cornea. The central corneas of uninfected and saline control nu/nu mice also were observed. This area in nu/nu mice exhibited an infrequent polymorphonuclear neutrophil (with no intracellular bacteria) and capillaries similar in size and location to those described for experimentally infected nu/nu mouse corneas. Untreated and saline control nu/+ mice, on the other hand, lacked both vessels and polymorphonuclear neutrophils in the central cornea.