To define the prevalence of impaired ventilatory responses in hypothyroidism, clinical and chemical parameters predicting their presence, and the potential for their acute reversal, ventilatory responses to hypercapnia and hypoxia were studied in 38 hypothyroid patients before treatment, and after short-term (seven days) and long-term (12 to 24 weeks) thyroid hormone therapy. Before treatment, hypercapnic ventilatory responses were blunted in 10 of 29 patients (34 percent), whereas hypoxic ventilatory responses were abnormal in eight of 30 patients (27 percent). Hypothyroid women and patients with marked pretreatment elevation of the serum thyrotropin concentration (greater than 90 mU/liter) were significantly more likely to have impaired ventilatory responses. In patients with an abnormal pretreatment response, parenteral thyroid hormone therapy (25 to 50 micrograms of L-triiodothyronine or 100 micrograms of L-thyroxine per day for seven days) significantly enhanced hypercapnic (0.75 +/- 0.06 to 1.19 +/- 0.16 liters/minute/mm Hg, p less than 0.05) and hypoxic (93 +/- 12 to 176 +/- 31 liters.mm Hg/minute, p less than 0.05) ventilatory responsiveness acutely. In seven of nine patients with abnormal pretreatment hypercapnic responses, and six of eight patients with abnormal hypoxic responses, normal ventilatory responsiveness was restored after one week of therapy. It is concluded that: (1) a subset of hypothyroid patients have blunted ventilatory responses to hypercapnia and/or hypoxia; (2) hypothyroid women and patients with a serum thyrotropin greater than 90 mU/liter more often manifest this abnormality; and (3) thyroid hormone therapy for one week reverses impaired ventilatory responses in hypothyroidism.