In a multi-centre, randomized, double-blind, placebo-controlled clinical trial over 3 years high dose sublingual specific immunotherapy with an extract of a 6-grass-pollen mixture showed a highly significant and clinically relevant improvement in patients with grass pollen rhinitis/-conjunctivitis with or without asthma and an increase in allergen specific antibodies (IgG1, IgG4) indicating immunological efficacy. A difference of 46% in mean symptom medication score between active and placebo group was seen. The treatment with the sublingual solution was well tolerated. High dose sublingual immunotherapy can therefore be considered as an efficient therapeutic option in the management of IgE-mediated allergic airway diseases.