Background: Specific immunotherapy is widely used to treat allergic rhinitis, but few large-scale clinical trials have been performed. Objective: We sought to assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with standard drug therapy. Methods: We performed a double-blind, randomized, placebo-controlled study of 410 subjects (203 randomized to 100,000 standardized quality units [SQ-U] maintenance, 104 to 10,000 SQ-U, and 103 to placebo). Three hundred forty-seven (85%) completed treatment. Groups were well matched for demographics and symptoms. Results: Across the whole pollen season, mean symptom and medication scores were 29% and 32% lower, respectively, in the 100,000–SQ-U group compared with those in the placebo group (both P