Alveolar hypoventilation is known to occur in myxedema. Reduction of hypercapnic ventilatory drive has not been reported, up to now, in patients with short-term hypothyroidism. Eleven patients with short-term hypothyroidism, before and after L-triiodothyronine (L-T3) replacement therapy, and 10 normal controls were studied. Hypercapnic ventilatory drive was assessed by the evaluation of the relation between the response of ventilation and mean expiratory flow to CO2 rebreathing and by the evaluation of ventilation and mean expiratory flow at a fixed level of carbon dioxide. In patients with short-term hypothyroidism these parameters were reduced as compared with normal controls and returned to normal after L-T3 replacement. We conclude that hypercapnic ventilatory drive is blunted by short-term hypothyroidism and normalizes following replacement therapy.