Normocapnic hyperpnea has been established as a method of respiratory muscle endurance training (RMET). This technique has not been applied on a large scale because complicated and expensive equipment is needed to maintain CO(2)-homeostasis during hyperpnea. This CO(2)-homeostasis can be preserved during hyperpnea by enlarging the dead space of the ventilatory system. One of the possibilities to enlarge dead space is breathing through a tube. If tube breathing is safe and feasible, it may be a new and inexpensive method for RMET, enabling its widespread use. The aim of this study was to evaluate the safety of tube breathing and investigate the effect on CO(2)-homeostasis in healthy subjects. A total of 20 healthy volunteers performed 10 min of tube breathing (dead space 60% of vital capacity). Oxygen-saturation, PaCO(2), respiratory muscle function, hypercapnic ventilatory response and dyspnea (Borg-score) were measured. Tube breathing did not lead to severe complaints, adverse events or oxygen desaturations. A total of 14 out of 20 subjects became hypercapnic (PaCO(2)>6.0 kPa) during tube breathing. There were no significant correlations between PaCO(2) and respiratory muscle function or hypercapnic ventilatory responses. The normocapnic versus hypercapnic subjects showed no significant differences between decrease in oxygen saturation (-0.7% versus -0.2%, respectively, P=0.6), Borg score (4.3 versus 4.7, P=0.9), respiratory muscle function nor hypercapnic ventilatory responses. Our results show that tube breathing is well tolerated amongst healthy subjects. No complaints, nor desaturations occurred. Hypercapnia developed in a substantial number of subjects. When tube breathing will be applied as respiratory muscle training modality, this potential development of hypercapnia must be considered.