Allergic rhinitis can be associated with bronchial hyperresponsiveness (BHR), and carries an increased risk for the development of asthma. The aim of this study was to evaluate the ability of specific immunotherapy (SIT) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR. Forty-four subjects monosensitized to Dermatophagoides pteronyssinus, with perennial rhinitis and BHR to methacholine, were randomly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr. After 1 yr of treatment, a 2.88-fold increase in the provocative dose of methacholine producing a 20% decrease in FEV(1) (PD(20)FEV(1)) was recorded in the SIT-treated group (95% confidence interval [CI]: 3.98- to 2.09-fold; p < 0.001), with a further increase to fourfold at the end of Year 2 (95% CI: 2.9- to 5.7-fold; p < 0.001). At the end of the study, the methacholine PD(20)FEV(1) was within the normal range in 50% of treated subjects (p < 0.0001), and was significantly higher in this group than in the group receiving placebo (p < 0.0001). In contrast, no changes in methacholine PD(20)FEV(1) were found in the placebo group throughout the study. Although 9% of subjects given placebo developed asthma, none of those treated with SIT did. This study suggests that SIT, when administered to carefully selected, monosensitized patients with perennial allergic rhinitis, reduces airway responsiveness in subjects with rhinitis, and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways.