To determine whether disodium cromoglycate (cromolyn) inhibits the bronchoconstriction produced by inhalation of sulfur dioxide (SO2) in people with asthma, we undertook a study of 6 asthmatic subjects. Each subject inhaled 40 mg of cromolyn on one day and lactose placebo on another day 20 min before inhaling SO2 for 10 min while exercising at a moderate rate (400 kpm/min) on a bicycle ergometer. Sulfur dioxide was delivered in humidified air at ambient temperature in concentrations of 0.5 ppm (3 subjects) or 1.0 ppm (3 subjects). Cromolyn and lactose treatments were given to each subject in a randomized sequence and in a double-blind manner. On a third day, each subject exercised at the same work rate breathing humidified air without SO2 at ambient temperature. We measured specific airway resistance (SRaw) in a body plethysmograph every 30 s for 10 min before and after each of the 3 periods of exercise. After treatment with lactose, SO2 inhalation significantly increased SRaw in all 6 subjects (from a baseline of 6.5 +/- 0.9 to 19.0 +/- 4.8 L x cm H2O/L/s (mean +/- SE) after SO2). After treatment with cromolyn, SO2 inhalation caused no increase in SRaw in 4 subjects and a small rise in 2 subjects. The mean increase in SRaw (from a baseline of 7.3 +/- 0.9 to 10.0 +/- 1.5 L x cm H2O/L/s after SO2) was significantly smaller than after lactose treatment (p less than 0.025). Exercise alone had no effect on SRaw in any subject. Thus, cromolyn inhibits SO2-induced bronchoconstriction in subjects with asthma. This finding suggests either that SO2 induces bronchoconstriction by stimulating the release of mediators from mast cells or that cromolyn inhibits bronchoconstriction by a mechanism independent of its effect on mast cells.