Allergic rhinitis is a widespread clinical problem, estimated to affect 20 to 40 percent of the population in the U.S. Inhalant allergens, such as plant pollens, characteristically cause seasonal rhinoconjunctivitis and/or asthma; whereas, cat dander, cockroaches, or dust mite allergens may induce symptoms year-round, and are associated with perennial rhinitis and/or asthma. The prevalence of asthma in the U.S. is approximately 9 percent, and approximately 62 percent of individuals with asthma show evidence of also having atopy (i.e., one or more positive-specific IgE levels). The medical management of patients with allergic rhinitis and asthma includes allergen avoidance, pharmacotherapy, and immunotherapy. Allergen-specific immunotherapy (SIT) is typically recommended for patients whose allergic rhinoconjunctivitis and asthma symptoms cannot be controlled by medication and environmental controls, for patients who cannot tolerate medications, or for patients who do not comply with chronic medication regimens. Currently, two forms of specific immunotherapy are used clinically in the U.S. The U.S. Food and Drug Administration (FDA) has approved the use of allergen extracts for subcutaneous administration (subcutaneous immunotherapy) for the treatment of seasonal and perennial allergic rhinitis and allergic asthma. In the U.S., a patient with allergies receives subcutaneous injections of an allergen-containing extract, comprised of the relevant allergens to which the patient is sensitive, in increasing doses, in an attempt to suppress or eliminate allergic symptomatology. Considerable interest has also evolved in using sublingual immunotherapy as an alternative to subcutaneous injection immunotherapy. Sublingual immunotherapy involves placement of the allergen under the tongue for local absorption to desensitize the allergic individual over a period of months to years and diminish allergic symptoms. In 1996, an Immunotherapy Task Force, assembled by the World Allergy Organization, cited the emerging clinical data on sublingual immunotherapy, recognized its potential as a viable alternative to subcutaneous therapy, and encouraged continued clinical investigation to characterize optimal techniques. Over the past two decades, sublingual forms of immunotherapy have gained favor in Europe; sublingual tablet immunotherapy has been approved by the European regulatory authorities. In the U.S., there are currently no FDA-approved sublingual forms of immunotherapy. In the absence of FDA-approved sublingual forms of immunotherapy, some researchers and physicians in the U.S. are exploring the off-label use of subcutaneous aqueous allergens for sublingual desensitization. An increasing number of U.S. physicians are employing this alternate desensitization approach in the treatment of allergic respiratory conditions based on European and U.S. studies, and on the European Medicines Agency's approval of certain oral products; however, due to differing standardization of potency in Europe and the United States, doses have been hard to translate between countries. The primary objective of this comparative effectiveness review is to evaluate the efficacy, effectiveness, and safety of SIT (including both subcutaneous and sublingual immunotherapy) that are presently available for use by clinicians and patients in the U.S. We addressed the following Key Questions (KQs): KQ1. What is the evidence for the efficacy and effectiveness of SIT in the treatment of allergic rhinoconjunctivitis and/or asthma? KQ2. What is the evidence for safety of SIT in patients with allergic rhinoconjunctivitis and/or asthma? KQ3. Is the safety and effectiveness of SIT different in distinct subpopulations with allergic rhinoconjunctivitis and/or asthma? Specifically: Children, Adults, Elderly, Pregnant women, Minorities, Inner-city and rural residents, Monosensitized individuals, Patients with severe asthma.