Background: House dust mite allergens play an important role in inducing IgE-mediated sensitization and the development of bronchial hyperresponsiveness (BHR) and asthma. This study investigated the relation shift between mite allergen exposure and the clinical activity and severity of asthma. Methods: Nonsmoking adult patients with asthma (n = 53) were randomly recruited from the asthma registry of two large family practitioner surgeries. Each participant underwent skin testing with common inhalant allergens, a methacholine bronchoprovocation test, and pulmonary function testing on up to 3 separate occasions over a 4-week period. BHR was expressed both as PD20 and dose-response ratio (DRR), and the patients with PD20 of less than 12.25 μmol methacholine were classified as methacholine reactors. Patients were also asked to record peak expiratory flow rate (PEFR) values at 2-hour intervals during waking hours for 1 month. Daily PEFR variability was calculated as amplitude percent mean. Dust samples were collected by vacuuming bedding, bedroom carpets and mattresses. In addition, in the homes of 32 subjects with positive skin test responses to mites, airborne samples were taken overnight for 8 hours with a personal sampler attached to each subject's pillow. Der p 1 and Der p 2 levels were determined by a two-site monoclonal antibody-based ELISA. Results: No difference in mite allergen exposure was found between subjects who were sensitive to mites and those who were not. However, mite-sensitive methacholine reactors were exposed to significantly higher concentrations of Der p 1 in beds than mite-sensitive methacholine nonreactors (13.2 μg/gm and 1.45 μg/gm, respectively; p <0.02). Der p 1 and Der p 2 were undetectable in 30 of 32 airborne samples. In mite-sensitive patients both Der p 1 and Der p 2 in beds significantly correlated with BHR (PD20. r = -0.49, DRR, r = 0.49; PD20: r = -0.46, DRR: r = 0.43) and amplitude percent mean PEFR (r = 0.38, r = 0.41) for Der p 1 and Der p 2, respectively. There was a significant negative correlation between exposure to Der p 1 and percent predicted FEV1 (r = -0.43). The correlation between Der p 2 and percent predicted FEV1 just failed to reach a significant level but showed a clear trend (r = -0.35, p = 0.068). Conclusions: Clinical activity and severity of asthma (measured by the level of BHR, PEFR variability, and percent predicted FEV1) in mite-sensitive patients is related to exposure to mite allergens in the dust reservoir, with levels in bed being an important indicator that correlated with disease activity.