Azelastine (CAS 58581-89-8) is a selective H1-receptor antagonist that inhibits histamine release and interferes with activation of other mediators of allergic inflammation. The present double-blind study aimed to evaluate azelastine eye drops (Allergodil) in patients with perennial allergic conjunctivitis compared to placebo. A total of 116 patients with an ocular symptoms score for itching and conjunctival redness > or = 3 (0-6 scale) were randomized to twice-daily 0.05% azelastine eye drops treatment (n = 58) or placebo. Patients maintained daily logs and were clinically evaluated after 7, 21 and 42 days of treatment. Azelastine significantly improved itching and conjunctival redness versus placebo (p < 0.001). Tolerability was rated good or better by 97% of patients with only bitter taste and application site reaction notable adverse experiences. On Day 7, ocular symptoms score improved by 1.5 +/- 0.9 (versus 0.5 +/- 0.8 placebo) with score improvement > or = 2 in 55% with azelastine (versus 14% placebo). Itching and redness further improved at Day 42 (score improvement > or = 2 in 95% with azelastine versus 33% placebo) and completely resolved for 47% azelastine patients (versus 10% placebo). Daily patient logs confirmed the clinically assessed scores. Topical azelastine progressively improved itching and conjunctival redness in patients with moderate to severe perennial allergic conjunctivitis. Continued improvement with prolonged use is consistent with mechanisms other than H1-receptor blockade, such as possible down regulation of adhesion molecule receptors.