The sulfidopeptide leukotrienes (LT) C4, D4, and E4 increase in nasal secretions during the nasal response to antigen challenge, and nasal challenge with LTD4 induces nasal congestion. To further assess the role of leukotrienes, we administered an oral LTD4 antagonist, L-649,923, to 12 patients who had nasal allergy to grass and ragweed pollen, in a double-blind, placebo-controlled, crossover study. Patients were challenged intranasally with increasing doses of pollen on each of 2 days, and the recovered nasal lavage fluids were assayed for histamine, TAME-esterase activity, and immunoreactive LTC4/D4/E4. The patients graded runny nose, congestion, and throat irritation, and sneezes were counted. Significant (p less than 0.01) increases in all parameters were found when comparing antigen challenge with diluent challenge, but no differences were seen among the treatment groups. Thus, oral L-649,923 was not effective in blocking the symptoms of the early nasal allergic response.