To determine whether the inhibitory effect of cromolyn on sulfur dioxide-induced bronchoconstriction is dose dependent, we compared the effects of treatment with 200 mg of cromolyn, with 20 mg of cromolyn, and with placebo on the rise in specific airway resistance provoked by inhalation of serially increasing concentrations of sulfur dioxide (0.25 to 8.0 ppm) in 10 asthmatic subjects. The geometric mean concentration of sulfur dioxide needed to cause an increase in SRaw of 8 L X cm H2O/L/s was significantly greater after 200 mg of cromolyn (1.98 ppm) than after 20 mg of cromolyn (0.94 ppm), which was in turn significantly greater than after placebo (0.35 ppm). We then examined whether the greater protection afforded by 200 mg of cromolyn was due to direct inhibition of smooth muscle contraction. We measured the bronchomotor response to the inhalation of serially increasing concentrations of methacholine aerosol (0.06 to 2.0 mg/ml) in 7 asthmatic subjects. Again, each subject was treated on 3 separate days with 200 mg of cromolyn, with 20 mg of cromolyn, and with placebo. We found that methacholine responsiveness was not decreased by either dose of cromolyn. We conclude that cromolyn inhibits sulfur dioxide-induced bronchoconstriction in a dose-dependent manner and that it does not directly inhibit smooth muscle responsiveness.