Three new procedures and apparatus for measuring the oxygen cost of breathing are described. Also presented are data on the O2 cost of breathing over the entire ventilatory range. It was observed that each breathing rate established a different O2 uptake-ventilation curve. An O2 uptake-ventilation curve produced by ‘optimum’ combinations of breathing rate and tidal volume (which are close to inherently chosen combinations) was shown to be composed of the ‘efficient’ segments of the O2 uptake-ventilation curves. As the maximum effort at any given breathing rate was approached the O2 cost per unit ventilation increased very rapidly producing a large range of O2 uptake values for subjectively equivalent ‘maximum’ efforts. It was therefore suggested that when used as a clinical test more uniform results could be expected if the breathing effort were less than maximum. A volume ‘deficit’ as a result of time ‘loss’ in flow reversal during the breathing cycle is introduced as a newly described factor affecting the work of breathing. It is shown that this factor results in increasing nonelastic work with increasing breathing rates at constant pulmonary ventilation. The opposite effect of increasing breathing rate on elastic and nonelastic work at constant pulmonary ventilation establishes an optimal breathing frequency for a given pulmonary ventilation. This optimal frequency may be determined from a family of O2 uptake-ventilation curves. It is also shown that this family of curves may be adjusted so as to also indicate the optimal breathing frequencies for various alveolar ventilations. An explanation is presented for the wide differences in previously reported O2 uptake-ventilation curves. Submitted on October 9, 1957