We compared the oxygen cost of breathing (Symbol) in healthy men and women over a wide range of exercise ventilations (Symbol). Eighteen subjects (nine women) completed 4 days of testing. First, a step-wise maximal cycle exercise test was completed for the assessment of spontaneous breathing patterns. Next, subjects were familiarized with the voluntary hyperpnoea protocol used to estimate Symbol. During the final two visits, subjects mimicked multiple times (four to six) the breathing patterns associated with five or six different exercise stages. Each trial lasted 5 min, and on-line pressure–volume and flow–volume loops were superimposed on target loops obtained during exercise to replicate the work of breathing accurately. At ˜55 l min−1Symbol, Symbol was significantly greater in women. At maximal ventilation, the absolute Symbol was not different (P > 0.05) between the sexes, but represented a significantly greater fraction of whole-body Symbol in women (13.8 ± 1.5 vs. 9.4 ± 1.1% Symbol). During heavy exercise at 92 and 100% Symbol, the unit cost of Symbol was +0.7 and +1.1 ml O2 l−1 greater in women (P < 0.05). At Symbol, men and women who developed expiratory flow limitation had a significantly greater Symbol than those who did not (435 ± 44 vs. 331 ± 30 ml O2 min−1). In conclusion, women have a greater Symbol for a given Symbol, and this represents a greater fraction of whole-body Symbol. The greater Symbol in women may have implications for the integrated physiological response to exercise.