Topical steroids potentiate Pseudomonas keratitis in the absence of concomitant antibiotic therapy. The effects of other anti-inflammatory agents on microbial keratitis are unknown, but if these agents do not intensify the infection, they may be useful in the initial management of microbial keratitis by limiting ulceration and thus the size of the resultant corneal scar. In rabbit models of untreated Pseudomonas keratitis and pneumococcal keratitis, topical 1% prednisolone phosphate, 0.03% flurbiprofen sodium, and vehicle were applied hourly. In cases of Pseudomonas keratitis, prednisolone worsened the clinical disease, and flurbiprofen further worsened the disease. When combined with effective antibiotic therapy, neither anti-inflammatory agent worsened the disease. In pneumococcal keratitis, neither anti-inflammatory agent worsened the disease. Topical anti-inflammatory agents should be used with caution in cases of microbial keratitis at least until effective antibiotic therapy has been instituted.