A double-masked, randomized, parallel group, placebo-controlled study demonstrated the efficacy of Naphcon-A (naphazoline HCl 0.025% and pheniramine maleate 0.3%). Seventy-two patients with a documented positive skin test or radioallergosorbent test were recruited. Three groups of 24 patients each received 1 drop of Naphcon-A instilled in one eye, and 1 drop of either naphazoline, pheniramine, or placebo in the other eye. After the instillation of test medication, a titrated dose of ragweed antigen was administered bilaterally, and ocular signs and symptoms were evaluated 10, 30, and 120 minutes later. All patients (excluding 4 who had persistent symptoms attributable to ragweed) were rechallenged with ragweed antigen at 120 minutes to assess the duration of action of the test medications. Naphcon-A was significantly more effective than placebo, naphazoline, and pheniramine in reducing redness. Naphcon-A and pheniramine were equally effective in relieving itching.