A 58-yr-old woman presented with recurrent chest infections, breathlessness, and orthopnea. She complained of nonspecific tiredness and aching limbs. A chest radiograph showed an elevated right hemidiaphragm. Thyroid function tests showed her to be severely hypothyroid (T4 = 23 nmol/L; TSH greater than 50 mU/L). Measurement of maximal respiratory mouth pressures (expiratory: 50 cm H2O, normal, 94 +/- 33; inspiratory: 15 cm H2O, normal, 71 +/- 27) suggested global respiratory muscle weakness. Severe bilateral diaphragm weakness was demonstrated by a greatly reduced maximal transdiaphragmatic pressure (Pdi) (Pdi Pimax = 0, normal, 65 +/- 31 cm H2O; sniff Pdi = 25 cm H2O, normal, 121 +/- 25). No Pdi was detectable on stimulation of the right phrenic nerve, whereas, on the left, it was 11 cm H2O (normal 7 to 15 cm H2O). Phrenic nerve conduction time was prolonged to both sides (right, 12 ms, left, 10 ms; normal, less than 9.5 ms). The relaxation rate of Pdi after a maximal sniff and after bilateral phrenic nerve stimulation was abnormally slow (7.4%/10 ms, 6.3%/10 ms, respectively). Three months after starting treatment with thyroxine she had become euthyroid, and phrenic nerve conduction times and Pdi relaxation rates had returned to normal. Maximal respiratory pressures, vital capacity, and maximal voluntary ventilation improved progressively on treatment, although maximal respiratory pressures still had not reached the normal range after six months. We conclude that hypothyroidism may present with breathlessness due to respiratory muscle weakness and/or phrenic nerve neuropathy and is reversible with treatment.