The intracellular adhesion molecule-1 (ICAM-1) is a reliable marker of allergic inflammation; its soluble isoform in serum is hypothesized to reflect the severity of the disease, therefore it may be used to monitor the efficacy of specific immunotherapy. We evaluated the levels of soluble ICAM-1 in the serum of 14 patients with grass-induced respiratory allergy before and after 12 months of specific immunotherapy, and correlated this parameter with the clinical outcome, measured using a visual analog scale. We found that in the majority of the patients, soluble ICAM-1 levels paralleled the clinical trend of the disease, with a significant decrease of soluble ICAM-1 in patients with successful specific immunotherapy (Spearman's correlation test: r = 0.57; p < 0.001). Therefore, we hypothesize that soluble ICAM-1 could be regarded as a reliable indirect marker of specific immunotherapy efficacy and that it could be used for monitoring clinical outcome.