Total respiratory resistance (R(T)) was measured by the application of a sine wave of airflow to the mouth at the resonant frequency of the respiratory system. The mean respiratory resistance of 42 normal subjects, measured at a mean functional residual capacity of 3.3 liters, was 2.3, SD +/- 0.5, cm H(2)O/liter per sec, and the resonant frequency was between 5 and 8 cycle/sec. The airway resistance measured in these same subjects with the body plethysmograph at a mean panting thoracic gas volume of 3.5 liters was 1.3, SD +/- 0.3, cm H(2)O/liter per sec. Total respiratory resistance was found to vary inversely with lung volume (V) measured plethysmographically; prediction formulae for normal subjects based on this relationship are: R(T) (mean) = 7.1/V, R(T) (range) = 4.0/V to 11.6/V where V is in liters and R(T) is in cm H(2)O/liter per sec. When these criteria were applied to subjects with thoracic disease the following results were obtained: 17 subjects with obstructive lung disease all had elevated total respiratory resistance; 9 subjects with diffuse lung disease without airway obstruction all had normal respiratory resistance; all but 1 of 5 obese subjects and all but 2 of a heterogeneous group of 9 subjects without airway obstruction had normal respiratory resistance. Failure to take lung volume into account resulted in a considerable decrease in the ability to discriminate between obstructive and nonobstructive lung disease on the basis of the forced oscillation test. The resonant frequency of the respiratory system of patients with obesity or nonobstructive lung disease was similar to that obtained in the normal group; accurate evaluation of resonant frequency in subjects with obstructive lung disease was frequently not possible. The combined resistances of lung, thoracic wall and abdominal tissues were found to account for less than 43% of the total respiratory resistance in normal subjects and were only slightly increased by the presence of obesity, restrictive diseases of the thoracic wall, and hyperinflation of the thorax. The forced oscillation method is potentially of value in the study of resistance to breathing of patients who cannot undergo body plethysmography, such as acutely ill, anesthetized, or unconscious subjects. Accurate evaluation of R(T) requires an independent measure of lung volume as well as careful attention during measurements to the airflow rate, phase of respiration, and the adequacy of cheek compression and laryngeal relaxation.