Usually, specific allergy-related plasma proteins such as immunoglobulin E (IgE) and immunoglobulin G (IgG) are used for estimating the grade of sensitization and follow-up of immunotherapy. In recent years, several nonspecific inflammatory markers, such as sICAM-1 and sIL-2R, have been shown as being suitable for therapy control in allergy. In our investigation of patients under sublingual immunotherapy (SLIT), plasma from 42 healthy controls and 133 children with single inhalation allergies to grass pollen, birch pollen or house dust mites was obtained during the symptom-free period. Patients showed symptoms including allergic rhinitis, dermatitis and allergic asthma with one single RAST class 3 or higher. Plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R), sE-selectin, interleukin-12 (IL-12) and specific IgG4 were analyzed with the ELISA technique. After 1 year of SLIT, concentrations of sICAM-1, sIL-2R and sE-selectin declined significantly when results from all patients were taken as one group. Regarding the single allergen groups, the sICAM-1 and sIL-2R decrease was significant in the grass and mite group, but not in the birch group, while the sE-selectin decline was only significant in the birch group after 1 year of SLIT, but not in the grass and the mite group. No difference was observed in IL-12 and IgG4 expression. In two groups of controls with a mean age of 9.5 versus 17.5 years, the analyzed parameters were not age-dependent. The increased proteins may be useful as additional markers for the evaluation of immunological effects and follow-up investigations of allergy therapies.