Recurrence of Pseudomonas keratitis during treatment with corticosteroids has been reported previously in humans. Rabbits with keratitis due to Pseudomonas aeruginosa or Streptococcus pneumoniae were treated with antibiotics and either vehicle, methylprednisolone acetate, flurbiprofen, or nordihydroguaiaretic acid (NDGA). Cultures performed after 7 days were negative, and antibiotics were discontinued. Two weeks later, Pseudomonas keratitis recurred in 6 of 7 (85.7%) steroid-treated rabbits, 1 of 8 (12.5%) flurbiprofen-treated rabbits, 1 of 8 (12.5%) NDGA-treated rabbits, and none of 8 vehicle-treated rabbits. None of the 31 rabbits infected with Streptococcus pneumoniae experienced recurrence. These data confirm the clinical observation that Pseudomonas keratitis may recur if antibiotic therapy is discontinued and corticosteroids are administered; the risk of recurrence appears to be much less with nonsteroidal antiinflammatory agents.