SummaryTheoretical modelling predicts that the concentrating effect of nitrous oxide (N 2 O) uptake on alveolar oxygenation is a persisting phenomenon at typical levels of ventilation -perfusion (V ⁄ Q) inhomogeneity under anaesthesia. We sought clinical confirmation of this in 20 anaesthetised patients. Arterial oxygen pressure (P a O 2 ) was measured after a minimum of 30 min of relaxant general anaesthesia with an inspired oxygen (F I O 2 ) of 30%. Patients were randomly allocated to two groups. The intervention group had N 2 O introduced following baseline blood gas measurements, and the control group continued breathing an identical F I O 2 in nitrogen (N 2 ). The primary outcome variable was change in P a O 2 . Mean (SD) in P a O 2 was increased by 1.80 (1.80) kPa after receiving a mean of 47.5 min of N 2 O compared with baseline conditions breathing O 2 ⁄ N 2 (p = 0.01). This change was significantly greater (p = 0.03) than that in the control group: + 0.09 (1.37) kPa, p = 0.83 and confirms the presence of significant persisting concentrating and second gas effects. The concentrating and second gas effects of nitrous oxide (N 2 O) uptake on the alveolar partial pressure of oxygen (O 2 ) and volatile agents were described by Eger and Stoelting [1, 2]. They detailed how these effects are produced by the initial rapid uptake of N 2 O for the first several minutes of an inhalational anaesthetic, during which time the rate of N 2 O uptake sharply declines. Subsequent authors have followed the effect on end-tidal and arterial partial pressures with serial measurements, and some authors have questioned the clinical validity of the phenomenon, at least in relation to its effect on volatile agent concentrations [3]. However, Nishikawa et al. found a measurable effect on end-tidal O 2 concentration and arterial oxygen tension (P a O 2 ) up to 30 min after commencement of N 2 O [4]. These largely descriptive studies have been variously uncontrolled for important physiological factors that might potentially influence the effect, such as cardiac output, ventilation-perfusion matching, or time.More recently, computer modelling of alveolar gas exchange predicted that the better arterial oxygenation that results may not be short lived, but may persist indefinitely [5,6]. This prolonged effect is only predicted to be significant in the presence of moderately severe degrees of ventilation-perfusion (V ⁄ Q) inhomogeneity, and is due to ongoing N 2 O uptake in low V ⁄ Q lung units [6]. These levels of V ⁄ Q inhomogeneity are typical of anaesthetised patients, even those with healthy lungs [7][8][9][10][11]. However, N 2 O accelerates absorption atelectasis in regions of low V ⁄ Q [12,13] and may worsen shunting