Nedocromil sodium, a pyranoquinoline decarboxylic acid derivative, is a new antiasthma compound undergoing clinical investigation. It has been shown to be effective in the management of asthma and to attenuate exercise-induced bronchoconstriction. We performed a randomized, double-blind, placebo-controlled, crossover study in 12 ragweed-sensitive subjects known to respond to inhaled ragweed antigen. On two study days, four to ten days apart, ragweed challenges were performed using a standard protocol 30 minutes after a single dose (two puffs of 2 mg/puff) of either active drug or placebo. The PD20 (20% fall in FEV1) for each treatment day was compared by parametric and nonparametric 2-period crossover analyses. Baseline FEV1 pre-drug and post-drug administration did not differ significantly between study days. On the nedocromil day, the mean +/- SD for log PD20 was 2.25 +/- 0.561 and on the placebo day, 1.73 +/- 1.048 (P = 0.04). There were no side effects associated with either treatment. These results demonstrate that nedocromil is effective in shifting the stimulus response curve to inhaled antigen in some ragweed-sensitive subjects. Its wide spectrum of efficacy against bronchoprovocation suggests it is useful in the treatment of hyperreactive airway disorders.