Four normal subjects and 5 patients with chronic obstructive pulmonary disease (COPD) (mean FEV1, 1.03 L) had frequency:force curves of their sternomastoid muscle measured before and 5 min after a 12-min walk on a flat treadmill, a progressive exercise test (normal subjects only), and a 10-min period of sustained maximal voluntary ventilation (SMVV). Before each test, all subjects had a normal frequency:force curve, and the ratio of the force response at 20 Hz to that at 50 Hz was normal. After SMVV, all the normal subjects and 4 of the 5 patients developed a greater than 15% fall in 20:50 ratio, and this was taken to indicate the presence of low frequency fatigue (LFF). During SMVV, all the subjects achieved minute ventilation greater than 70% of predicted maximal breathing capacity (MBC). During the 12-min walk, all the patients exceeded 70% MBC, and 4 developed LFF. The normal subjects performing progressive exercise also exceeded 70% MBC, and all showed LFF. The 12-min walk did not cause LFF in the normal subjects, but no subject reached 70% of MBC. Despite the presence of LFF in the sternomastoid muscle, the patients were all able to walk the same distance during a second 12-min walk. In both the normal and patient groups, the ventilatory response to CO2 was not changed by the presence of LFF. There were no changes in maximal inspiratory and expiratory mouth pressures or spirometry with LFF. High, sustained levels of minute ventilation cause sternomastoid LFF, but the clinical significance of this phenomenon is not yet certain.