To determine under what circumstances the use of mechanical insufflation-exsufflation (MI-E) can generate clinically effective expiratory flows for airway clearance (> 2.7 L/s) for clinically stable patients with amyotrophic lateral sclerosis (ALS). Twenty-six consecutive patients with ALS were studied, 15 with severe bulbar dysfunction. Using a pneumotachograph and with the aid of an oronasal mask, we measured FVC, FEV(1), peak cough flow (PCF), maximum insufflation capacity (MIC), PCF generated from a maximum insufflation MIC (PCFMIC), and PCF generated by MI-E (PCFMI-E). MI-E was delivered at +/- 40 cm H(2)O. Maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) at the mouth were also measured. Although both groups had a similar time from ALS symptom onset to diagnosis, statistical differences (p < 0.05) were found between nonbulbar and bulbar patients in lung function and cough capacity parameters: FVC, 2.58 +/- 1.24 L vs 1.62 +/- 0.74 L; FEV(1), 2.26 +/- 1.18 L vs 1.54 +/- 0.69 L; PImax, - 93.45 +/- 47.47 cm H(2)O vs - 3.64 +/- 25.07 cm H(2)O; PEmax, 140.45 +/- 75.98 cm H(2)O vs 69.93 +/- 32.14 cm H(2)O; MIC, 3.02 +/- 1.22 L vs 1.97 +/- 0.75 L; PCF, 5.91 +/- 2.55 L/s vs 3.42 +/- 1.44 L/s; PCFMIC, 6.68 +/- 2.71 L/s vs 4.00 +/- 1.48 L/s; and PCFMI-E, 4.34 +/- 0.82 L/s vs 3.35 +/- 0.77 L/s. Four patients with bulbar dysfunction and MIC > 1 L had PCFMI-E < 2.7 L/s. The receiver operating characteristic (ROC) curve analysis showed PCFMIC of <or= 2.7 L/s predicting those patients with PCFMI-E < 2.7 L/s. The ROC curve analysis showed PCFMIC > 4 L/s predicting those patients with PCFMIC greater than PCFMI-E. MI-E is able to generate clinically effective PCFMI-E (> 2.7 L/s) for stable patients with ALS, except for those with bulbar dysfunction who also have a MIC > 1 L and PCFMIC <2.7 L/s who probably have severe dynamic collapse of the upper airways during the exsufflation cycle. Clinically stable patients with mild respiratory dysfunction and PCFMIC > 4 L/s might not benefit from MI-E except during an acute respiratory illness.