Background: Allergen specific immunotherapy is aimed at modifying the natural history of allergy by inducing tolerance to the causative allergen. In its traditional, subcutaneous form, immunotherapy has complete evidence of efficacy in allergic asthma. However, subcutaneous immunotherapy (SCIT) has a major flaw in side effects, and especially in possible anaphylactic reactions, and this prompted the search for safer ways of administration of allergen extracts. Sublingual immunotherapy (SLIT) has met such need while maintaining a clinical efficacy comparable to SCIT. Objectives: We aimed to investigate immunological efficacy of mite-specific SLIT and SCIT versus a placebo in asthmatic patients who were sensitized to house dust mite: Dermatophagoides farinae (D.farinae).Methods: This study is a prospective, randomized, three parallel group studies, comparing the clinical and immunological efficacy of SLIT and SCIT, with (D.farinae) allergen to that of placebo in treatment of patients with allergic asthma and a proven allergy to (D.farinae) by skin prick test. 60 patients mono-sensitized to (D.farinae) were randomized to receive either SLIT (n=30), SCIT (n=15) or Placebo (n=15). Symptom and medication score, serum (D.farinae) specific immunoglobulin E (IgE), IL4, IL-10 and IFN-γ levels were evaluated at base line and after three months.Results: SLIT and SCIT demonstrated a significant reduction in asthma symptom and medication score. A significant reduction of serum-specific D.farinae IgE in SLIT and SCIT were observed. Serum IL-10 and IFN-γ significantly increased in SLIT and SCIT compared with placebo, whereas serum IL-4 significantly decreased. No statistically significant change was observed when SLIT compared to SCIT either in clinical or immunological parameter. Conclusion: Both SLIT and SCIT demonstrated clinical and immunological improvement compared to placebo in asthmatic patients monosensitized to D. farinae.