We studied 16 asthmatic subjects sensitive to changes in airway osmolarity to determine whether nedocromil sodium has any effect on airway narrowing caused by hypertonic saline challenges. Nedocromil sodium (10 mg) or its vehicle was inhaled 10 min before a challenge with ultrasonically nebulized 4.5% NaCl. FEV1 was measured before challenge and 1 min after each challenge period of 0.5, 1, 2, 4, 8, 8 and 8 min. The challenge was stopped when there was a 20% fall in FEV1 from baseline or after the final challenge period. We measured airway sensitivity, that is, the provoking dose of 4.5% NaCl required to induce a 20% reduction in FEV1 (PD20FEV1) and calculated the fold difference in PD20FEV1 after the intervention. After inhaling nedocromil sodium there was a 3.95-fold improvement in PD20 (p < 0.001) when compared with the vehicle day. After pretreatment with nedocromil sodium two of the 16 subjects were completely protected against 4.5% NaCl challenge, and six developed a plateau in their response. We conclude that nedocromil sodium is effective in reducing airway narrowing in response to 4.5% NaCl challenge in asthmatic subjects, and it appears to be unique in its ability to produce a plateau in response to acute administration of a drug before a bronchial challenge.