We studied the effect of changing the duration of isocapnic hyperventilation on the time course of bronchoconstriction in five subjects with asthma. Each subject performed hyperventilation challenges of 4, 8, and 16 min. No significant bronchoconstriction occurred until the hyperventilation was stopped, regardless of its duration. We found increased bronchoconstriction as the duration of hyperventilation increased. The declines in FEV1 (mean +/- SD) from baseline were 13 +/- 10%, 22 +/- 7%, and 29 +/- 12% for 4, 8, and 16 min of hyperventilation, respectively (1 versus 3, p less than 0.01). Mean times after hyperventilation until maximal bronchoconstriction were 12 +/- 4 min, 9 +/- 6 min, and 6 +/- 4 min. We also found slight bronchodilation during the first 4 min of hyperventilation. After 2 and 4 min of hyperventilation, the FEV1 was 103 +/- 5% and 103 +/- 3% of baseline, respectively (both p less than 0.05, compared to baseline). We conclude that increasing the duration of hyperventilation delays the onset of bronchoconstriction but causes greater bronchoconstriction once the hyperventilation is stopped. These results suggest that either hyperventilation itself inhibits bronchoconstriction or that the mechanisms that induce bronchoconstriction in response to hyperventilation operate after, rather than during, hyperventilation.