To determine the role of familial factors in the hypoventilation of chronic obstructive lung disease we measured chemical drives to breathe in normal offspring of two groups of patients with an equal degree of obstruction. One group of five patients had repeatedly normal arterial carbon dioxide tension (PaCO2), whereas PaCO2's were elevated in the other group of six. Two adult offspring of each patient were studied. Drives were measured as the ventilatory response to isocapnic hypoxia, and the slopes of the ventilation/PCO2 relation (the hypercapnic ventilatory response). The mean response to isocapnic hypoxia was lower (P less than 0.01) in offspring of patients with high PaCO2's than in the offspring of patients with normal levels (71 +/- 7.8 [S.E.M.] vs. 113 +/- 10.3); one offspring of each patient with high PaCO2 had a response below the range found in offspring of all patients with normal PaCO2. Lower hypercapnic ventilatory responses (P less than 0.05) were also found in the offspring of patients with high PaCO2. Familial factors in the control of breathing may be an important determinant of ventilation in chronic obstructive lung disease.