This study tested the capability of a single 42-mu g dose of inhaled salmeterol xinafoate, a long-acting Pz-agonist, to protect against bronchoconstrictive effects of exposure to 0.75 ppm sulfur dioxide (SO2) during exercise, for up to 24 h, Ten SO2-responsive adult volunteers with stable asthma were studied under 4 conditions of drug pretreatment/exposure, administered in random order, double-blind: salmeterol/SO2, placebo/SO2, salmeterol/clean air, and placebo/clean air, Each subject underwent 10-min exposure/exercise challenges in a chamber 1, 12, 18, and 24 h after pretreatment, Exercise ventilation rates averaged 29 L/min, Response was measured as the decrement in FEV(1) between preexposure and postexposure (lowest value within 30 min), After salmeterol, mean decrement post-SO2 was 7% at 1 h and 12% at 12 h. At 18 and 24 h after salmeterol, and at all times after placebo, mean decrements were 25 to 30%. After 18 and 24 h, salmeterol still improved baseline FEV(1) relative to placebo, although improvement was not statistically significant at 24 h, Acute symptom increases accompanied FEV(1) decrements, Conclusion: In our asthmatic subjects, pretreatment with salmeterol imparted clinically and statistically significant (p < 0.01) protection against bronchoconstriction induced by SO2/exercise for at least 12 h, and maintained an improvement in lung function for as much as 18 h.