The objective of this study was to evaluate the efficacy of 0.05% levocabastine, a new antihistamine formulated for ophthalmic use, compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge. Subjects who reacted. positively in both eyes on two separate occasions to ocular allergen challenge with grass, ragweed, or cat dander (N = 47) received one dose of 1 to 2 drops of 0.05% levocabastine in one eye and its vehicle in the other eye. After 10 minutes, the predetermined dose of allergen was instilled in both eyes. Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and reevaluated to determine levocabastine's duration of action. Results showed that levocabastine was significantly more effective than placebo in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later (p < 0.05). These results demonstrate that levocabastine, currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor, is efficacious in the inhibition of itching, as well as all of the allergic signs of a vascular origin, with a duration of action of at least 4 hours. Because of its strong effects on itching and hyperemia, chemosis, lid swelling, and tearing, levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis.