The combination of acute hypoxia and increased respiratory load is encountered in several respiratory diseases including acute life-threatening asthma and sleep apnea. Hypoxia has been shown to inhibit respiratory load perception in healthy and asthmatic subjects, and could contribute to treatment delays and impaired function of protective reflexes.Using respiratory-related evoked potentials (RREPs) this study aimed to determine the sensory processes mediating hypoxia-induced suppression of respiratory load sensation.EEG was measured over the central and parietal cortical regions in 14 healthy subjects. RREPs were elicited by 500-ms midinspiratory resistive load stimuli during and after isocapnic normoxia or hypoxia (blood arterial O2 saturation approximately 80%). On a separate occasion, subjects rated the perceived magnitude of five externally applied inspiratory resistive loads (range, 8.6-43.7 cm H2O x L(-1) x s) under similar experimental conditions. In both experiments subjects voluntarily ventilated approximately 90% above baseline to match ventilatory output between gas conditions.RREP stimulus was matched between gas conditions in 11 subjects (minimum mask pressure -9.7 +/- 0.6 versus -9.2 +/- 0.4 cm H2O). P1 and P2 amplitudes were reduced during isocapnic hypoxia compared with normoxia (maximal at Cz: P1, 2.5 +/- 1.1 versus 3.9 +/- 1.2 microv, p = 0.03; P2, 10.0 +/- 2.2 versus 12.4 +/- 2.1 microv, p < 0.01, respectively). Perceived magnitude of externally applied resistive loads was also reduced during hypoxia compared with normoxia (17.1 +/- 1.1 versus 19.0 +/- 1.1 au, p < 0.01).These data confirm that isocapnic hypoxia suppresses respiratory load sensation. Decreased amplitude of the earlier (P1) RREP component suggests that this is mediated, at least in part, by suppression of respiratory afferent information before its arrival at the primary sensory cortex.