The present study evaluated the steroid-sparing effect of subcutaneous SQ-standardized specific immunotherapy (SIT) in moderate and severe house dust mite (HDM) allergic asthmatics. Fifty-four adult asthmatics allergic to HDM requiring at least inhaled corticosteroids (ICS) doses equivalent to 500 microg fluticasone propionate daily were randomized to subcutaneous SIT or placebo injections for a period of 3 years. The minimum required ICS dose, 4 week diary of asthma symptom score, use of rescue medication, peak expiratory flow (PEF) measurements and visual analog scale for asthma symptoms were assessed before start of treatment and after 1, 2 and 3 years of treatment. In patients with moderate and severe asthma, the reduction in ICS was statistical significant after 2 years of treatment (P = 0.03) but not after 3 years. The median reductions were 82% and 42% after the third year for active and placebo respectively. In patients with moderate persistent asthma the reduction was statistical significant larger for those treated with SIT compared with placebo after year 2 and year 3. The median reductions after 3 years were 90% for SIT and 42% for placebo (P = 0.04). Despite significant steroid reduction, there was no difference in asthma assessments between the two groups. No serious reactions related to SIT injections were seen. This study shows that SIT with a SQ-standardized HDM extract is safe. An ICS sparing effect was evident in patients with moderate persistent asthma.