Upper airway unidirectional breathing, nose in and mouth out, is used by panting dogs to facilitate heat removal via water evaporation from the respiratory system. Why some humans instinctively employ the same breathing pattern during respiratory distress is still open to question. We hypothesized that 1) humans unconsciously perform unidirectional breathing because it improves breathing efficiency, 2) such an improvement is achieved by bypassing upper airway dead space, and 3) the magnitude of the improvement is inversely proportional to the tidal volume. Four breathing patterns were performed in random order in 10 healthy volunteers first with normal breathing effort, then with variable tidal volumes: mouth in and mouth out (MMB); nose in and nose out (NNB); nose in and mouth out (NMB); and mouth in and nose out (MNB). We found that unidirectional breathing bypasses anatomical dead space and improves breathing efficiency. At tidal volumes of approximately 380 ml, the functional anatomical dead space during NMB (81 +/- 31 ml) or MNB (101 +/- 20 ml) was significantly lower than that during MMB (148 +/- 15 ml) or NNB (130 +/- 13 ml) (all P < 0.001), and the breathing efficiency obtained with NMB (78 +/- 9%) or MNB (73 +/- 6%) was significantly higher than that with MMB (61 +/- 6%) or NNB (66 +/- 3%) (all P < 0.001). The improvement in breathing efficiency increased as tidal volume decreased. Unidirectional breathing results in a significant reduction in functional anatomical dead space and improvement in breathing efficiency. We suggest this may be the reason that such a breathing pattern is preferred during respiratory distress.