Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure. We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS. Eighteen atopic asthmatic adolescents (12-18 yr, 500-2000 microg ICS daily) with established house dust mite allergy, participated in a parallel-group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10-week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups. During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U-EPX), leukotriene E4 (U-LTE4) and 9alpha11beta prostaglandin F2 (U-9alpha11beta PGF2) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U-EPX (P < 0.05) and U-LTE4 (P < 0.05) were maintained. A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long-acting beta2-agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short-term, rigorous allergen avoidance can improve the long-term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.