The presence of a peripheral myopathy in hypothyroidism has been well recognized. Involvement of the diaphragm has been suggested recently but the clinical spectrum never clearly defined. We studied three patients with hypothyroidism presenting with fatigue, dyspnea, exercise limitation, and in two, chronic alveolar hypoventilation (PaCO2 of 51 and 75 mm Hg) before and after thyroid hormone replacement. In all patients diaphragmatic strength as determined by the maximal transdiaphragmatic pressure was low (2, 13, and 64 cm H2O) and improved with therapy (86, 84, and 90 cm H2O). Similarly, all patients manifested a fatiguing breathing pattern, as determined by the diaphragmatic tension time index. These values (0.22, 0.55, and 0.36) decreased after hormone replacement (0.16, 0.20, and 0.15). These changes were associated with the correction of hypercarbia in the two patients with hypoventilation and an improvement in lung volumes and exercise endurance in all patients. This study confirms that in patients with hypothyroidism diaphragmatic dysfunction occurs more frequently than has been suspected and might be of varying severity. This dysfunction reverses with adequate hormone replacement.