Recent evidence has demonstrated a marked anticollagenolytic effect for the tetracycline antibiotics. We have examined the efficacy of systemic tetracycline hydrochloride in a rabbit model of corneal ulceration. A standard alkali burn (1N sodium hydroxide for 40 s) was delivered to 62 eyes (31 rabbits). Animals were then divided into three groups: group 1 (controls) (ten rabbits [20 eyes]) received no treatment; group 2 (ten rabbits [20 eyes]) received 10 mg/kg/d of tetracycline hydrochloride, given intramuscularly; and group 3 (11 rabbits [22 eyes]) received 50 mg/kg/d. Ulceration occurred in 85% (17/20) of control eyes. The higher dosage of tetracycline was more effective in preventing ulceration than the lower dosage (9.1% vs 55%). Eyes with higher levels of tetracycline in ocular tissues were less likely to ulcerate.