Reduced bronchodilatation in response to deep inspiration (DI) has been demonstrated in asthmatics. We have previously shown that inhibition of DI for 10 min or more during methacholine inhalation increases airway narrowing in normals. We tested the hypothesis that inhibition of DIs during methacholine inhalation in asthmatics would not affect the magnitude of airway narrowing. We administered the PC(15) dose of methacholine to eight asthmatics every 5 min for 5 doses and measured spirometry after each dose. On four separate days, subjects received either 2, 3, 4, or 5 doses selected randomly, but DIs were inhibited during the challenge and spirometry was measured only at the start and after the final dose. Geometric mean PC(15) was 1.6 mg/ml. Mean values for FEV(1) (+/- SEM) after Doses 2 through 5 were 84 +/- 4, 78 +/- 6, 79 +/- 5, and 81 +/- 3% of baseline, respectively, when DIs were allowed. During inhibition of DIs, they were 73 +/- 6, 67 +/- 5, 64 +/- 6, and 61 +/- 7% of baseline values. Decreases in FEV(1) after Doses 4 and 5 were significantly greater when DIs were inhibited (p < 0.05). We conclude that in this group of asthmatics, inhibition of DI for 15 min is associated with increased airway narrowing in response to methacholine inhalation, and therefore, DI may be an important factor limiting induced airway narrowing in asthmatics as well as in normal subjects.