We used a rabbit model to investigate the pathogenesis of soft contact lens-induced bacterial keratitis. Rabbit eyes underwent complete tarsorrhaphy for 7 days either with (group A, n = 14) or without (group B, n = 13) new sterile soft contact lenses. On day 7, an increase in mean corneal thickness (20.3% in group A and 17.2% in group B) was detected. New or rabbit-worn soft contact lenses were then inoculated with 10(7) colony-forming units of Pseudomonas aeruginosa or by 0.1 mL of P aeruginosa suspension. On day 9, conjunctival cultures of all eyes yielded P aeruginosa. Corneal infection developed in 11 of 14 eyes wearing new or worn, contaminated soft contact lenses. Bacterial keratitis did not develop in any of the 13 eyes inoculated with P aeruginosa suspension. Light and electron microscopy of infected eyes showed abundant polymorphonuclear neutrophils destroying the epithelium, basement membrane, and stroma. Few bacteria could be detected and only in the deep stroma. Since bacterial suspension alone caused no inflammation, soft contact lens-wear appears crucial to corneal infection in this model.