Fothergill, D. M., and N. A. Carlson. Effects of N₂O narcosis on breathing and effort sensations during exercise and inspiratory resistive loading. J. Appl. Physiol. 81(4): 1562-1571, 1996.The influence of nitrous oxide (N₂O) narcosis on the responses to exercise and inspiratory resistive loading was studied in thirteen male US Navy divers. Each diver performed an incremental bicycle exercise test at 1 ATA to volitional exhaustion while breathing a 23% N₂O gas mixture and a nonnarcotic gas of the same PO₂, density, and viscosity. The same gas mixtures were used during four subsequent 30-min steady-state submaximal exercise trials in which the subjects breathed the mixtures both with and without an inspiratory resistance (5.5 vs. 1.1 cmH₂O ^· s ^· l¹ at 1 l/s). Throughout each test, subjective ratings of respiratory effort (RE), leg exertion, and narcosis were obtained with a category-ratio scale. The level of narcosis was rated between slight and moderate for the N₂O mixture but showed great individual variation. Perceived leg exertion and the time to exhaustion were not significantly different with the two breathing mixtures. Heart rate was unaffected by the gas mixture and inspiratory resistance at rest and during steady-state exercise but was significantly lower with the N₂O mixture during incremental exercise (P < 0.05). Despite significant increases in inspiratory occlusion pressure (13%; P < 0.05), esophageal pressure (12%; P < 0.001), expired minute ventilation (4%; P < 0.01), and the work rate of breathing (15%; P < 0.001) when the subjects breathed the N₂O mixture, RE during both steady-state and incremental exercise was 25% lower with the narcotic gas than with the nonnarcotic mixture (P < 0.05). We conclude that the narcotic-mediated changes in ventilation, heart rate, and RE induced by 23% N₂O are not of sufficient magnitude to influence exercise tolerance at surface pressure. Furthermore, the load-compensating respiratory reflexes responsible for maintaining ventilation during resistive breathing are not depressed by N₂O narcosis.