To determine whether abnormal chemical drives to breathe in patients with chronic obstructive pulmonary disease (COPD) antedate the development of chronic CO2 retention, we measured ventilatory and P0.1 responses to hypercapnia and hypoxia in 14 such patients and 23 of their normal adult offspring. Hypoxic responses in the patients were positively correlated with the mean hypoxic responses of their offspring. Neither the hypercapnic responses nor the resting breathing patterns of the patients were related to those of their offspring. Hypoxic response was lower in offspring of hypercapnic patients than in offspring of normocapnic patients. Blunt hypoxic responses in patients with COPD are influenced by familial factors and may represent a premorbid "risk factor" in the development of CO2 retention in this disease. This does not appear to be true for hypercapnic response or breathing pattern.