Three methods of quantitating the respiratory response to acute hypoxia were compared in nine normal young men: 1) Steady state CO 2 response at P O 2 = 200 and 40 torr. 2) Progressive hypoxia with PA CO 2 held at the subjects resting value and 5 torr- above this. 3) A single breath test which uses a single vital capacity inspiration of a hypoxic and/or hypercapnic gas and is presumed to stimulate primarily peripheral chemoreceptors. In methods 1 and 2 the ventilatory response to hypoxia (defined as the increment in ventilation produced by reduction of Pa O 2 from above 200 to 40 torr measured at the subjects' normal or standardized arterial P CO 2 ) averaged 19.9 and 20.9 L(min × m 2). Ventilation (mean of 2nd and 3rd spontaneous breaths) following a single vital capacity breath of 15% CO 2 in N 2 averaged 30.3 L(min × m 2) more than after a control breath of 5 % CO 2 on O 2. Hypoxic depression of ventilation occurred in 3 subjects during testing with method 1 and in 1 subject with method 2.