To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double-blind, placebo-controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo-treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo- and verum-treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum-treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite-allergen-induced asthma may reduce not only immediate, IgE-mediated symptoms but, after a rather long time period of 12–18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity.