1) Measured during spontaneous breathing in ten patients with diffuse interstitial lung disease, total pulmonary resistance averaged 3.53 +/- 1.56 cm H(2)O per L per second; airway resistance, 1.63 +/- 0.79 cm H(2)O per L per second; and lung tissue resistance, 1.90 +/- 0.95 cm H(2)O per L per second (range, 0.89 to 3.96). The lung tissue resistance was on an average about four times higher in patients with lung fibrosis than in ten healthy persons of the same age. No significant difference in airway resistance was found between healthy subjects and patients.2) In three patients the lung tissue resistance was measured during spontaneous breathing and during panting. Much higher values were found during spontaneous breathing.3) In patients with lung fibrosis and also in healthy subjects, there seems to have been an inverse correlation between the vital capacity, or the compliance, on the one hand, and the lung tissue resistance on the other. Nevertheless, in patients with lung fibrosis the lung tissue resistance was more increased than could be attributed to the loss of normally compliant lung tissue only.4) No correlation was found between the lung tissue resistance and severity of impairment of pulmonary gas exchange; especially no relationship appeared to exist between the lung tissue resistance and the alveolar-end capillary PO(2) gradient during hypoxia. This result indicates that the pathological alterations producing a measurable end gradient in hypoxia may be independent of the augmentation of the fibrous framework responsible for the stiffening of the lung.