Cysteinyl leukotrienes (CysLTs) are a key element of allergic inflammation. Thus, the antagonism of CysLTs appears a potential target of allergic rhinitis management. Antileukotrienes and antihistamines combined showed a synergistic effect in treating seasonal allergic rhinitis (SAR). This double blind, parallel group, randomized study aimed at evaluating the clinical and anti-inflammatory effects exerted by two combinations of antihistamine plus antileukotriene in patients with SAR and mild intermittent asthma. Thirty patients were treated with montelukast added to cetirizine (M-C group) or desloratadine (M-D group) for 2 weeks. The visits, including spirometry, nasal scraping and lavage, were performed in all subjects before and directly after the treatment. Evaluation parameters were: i) nasal symptoms, ii) number of eosinophils and neutrophils, and iii) IL5 and IL8 levels. Both combinations significantly reduced: nasal symptoms (p<0.001), eosinophils and neutrophils (p<0.001), IL5 (p<0.001 for M-C groupand p<0.01 for M-D group), and IL8 levels (p<0.001 for M-C group and p<0.05 for M-D group). M-C combination reduced more significantly than M-D combination: nasal symptoms (p<0.01), inflammatory cells (p<0.01), and cytokines (p<0.01). The present study demonstrates that these antileukotriene-antihistamine combinations are effective in relieving nasal symptoms in SAR. Moreover, these combinations exert additional anti-inflammatory activity as provided by reduction of inflammatory infiltrate and cytokine levels. Finally, cetirizine might exert more beneficial activity than desloratadine when added to montelukast.