A sex-, age-, obesity, and protease inhibitor-matched study of pulmonary function and ventilatory control was performed on 26 sons of 19 patients with chronic obstructive pulmonary disease (COPD) and 26 control subjects. Mean values for FEV1/FVC and V25 were significantly lower and CV/VC was significantly higher in sons of patients than in the controls. VC, airway resistance, static pulmonary compliance. delta N2, arterial blood gases and pH were not different between sons and controls. When the sons of patients were divided into two groups according to the arterial blood gases of their parents, sons of hypoxemic, hypercapnic parents showed significantly lower hypoxic ventilatory responses than sons of normoxemic, normocapnic parents. Hypercapnic ventilatory responses were not different between sons and controls. Abnormal pulmonary function and low ventilatory responses were more frequently detected in sons than in controls. The association of smoking with abnormalities of pulmonary function was not clearly seen in sons. These results suggest that familial factors (either genetic or environmental) play a significant role in determining the pathogenesis and clinical types of COPD.