Twelve children with allergic rhinitis due to monosensitivity to Dermatophagoides pteronyssinus (Dp) took part in a placebo-controlled, double-blind, crossover study to evaluate the effect of cetirizine, a second-generation, nonsedating H1-blocker-type antihistamine, on sulfidoleukotriene releasability by blood leukocytes and to determine its correlation with clinical findings and nasal challenge scores. Sulfidoleukotriene release by blood leukocytes was determined by the cellular allergen stimulation test (CAST), which measures leukotriene (LT)C4, LTD4, and LTE4, all in one assay. Compared to placebo, cetirizine significantly (P < 0.05) decreased daily symptom scores of nasal discharge, nasal itching, and sneezing, as well as the number of sneezings after nasal challenge with the antigen, without alleviating nasal obstruction (P > 0.05). It also suppressed both early (P < 0.05) and late skin reactions to intradermal tests. Although cetirizine did not influence in vitro sulfidoleukotriene production by blood leukocytes with buffer or anti-IgE (P > 0.05), it substantially reduced the release of these mediators upon challenge with Dp antigen. Furthermore, there was a high correlation between the number of sneezes after challenge and the amount of sulfidoleukotriene released in nine patients (r = 0.78; P < 0.01). It is concluded that the amount of sulfidoleukotrienes produced by blood leukocytes in vitro may reflect the nasal hyperreactivity of the patient, and that cetirizine, which is highly effective in the treatment of allergic rhinitis, owes part of its effect to inhibition of sulfidoleukotriene releasability by blood leukocytes in children.