SummaryThe relative order of potency of anaesthetic agents on the hypoxic ventilatory response has been tested in humans, but animal data are sparse. We examined the effects of 1.4, 1.6, 1.8, and 2.0 MAC halothane, isoflurane, and sevoflurane on phrenic nerve activity in euoxia (baseline) and during acute normocapnic hypoxia (inspired oxygen fraction 0.09) in adult male Sprague-Dawley rats. With halothane, all animals became apnoeic even in euoxia, and the hypoxic response was completely abolished at all anaesthetic levels. With isoflurane, 5 of 14 animals exhibited phrenic nerve activity in euoxia at 1.4 MAC and demonstrated a hypoxic response (302% of baseline activity), but all became apnoeic and lost the hypoxic response at higher doses. With sevoflurane, phrenic nerve activity and a hypoxic response was preserved in at least some animals at all doses (i.e. even the highest dose of 2.0 MAC). Similar to the rank order of potency previously observed in humans, the relative order of potency of depression of the hypoxic ventilatory response in rats was halothane (most depressive) > isoflurane > sevoflurane (p = 0.01 for differences between agents). Breathing is precisely controlled by the brain and its sensory inputs to maintain arterial blood gases and acidbase balance within narrow limits at rest and during exercise, to counteract threats to body homeostasis. Volatile anaesthetics change the pattern (rhythm, rate, and depth) of breathing at clinically relevant concentrations [1][2][3][4][5]. The influence of volatile anaesthetics on resting ventilation is dose dependent and depression becomes clinically relevant at high doses > 1.0 MAC [6]. However, the acute ventilatory response to hypoxia is much more sensitive and can be markedly depressed even by subanaesthetic concentrations (0.1 MAC) in humans. The exact mechanism of this effect remains elusive [2]. Acute hypoxia activates peripheral -but not centralchemoreceptors [7][8][9], and volatile anaesthetic agents have been shown to have a greater depressive effect on peripheral chemosensitivity to hypoxia than on central chemosensitivity to CO 2 [10][11][12].Pandit et al. [13][14][15] recently proposed a general order of potency for various volatile anaesthetics with respect to the acute ventilatory response to hypoxia in humans, with halothane the most potent in depressing it [2,16] and sevoflurane probably the least [17,18], while isoflurane showed an intermediate level of depressive effect [19][20][21]. There is considerable scope for clinical ⁄ human work in this area to confirm or refute this suggestion. However, since the exact mechanisms for these anaesthetic effects are unknown, there is also scope for carefully conducted,