Ten healthy young males were studied with a double-blind, cross-over trial to determine whether or not chlormadinone acetate (CMA), a potent synthetic progesterone, augments hypoxic chemosensitivity. Seven days after CMA administration, inspiratory minute volume (VI) and tidal volume (VT) significantly increased. PaCO2 decreased by 3.0 +/- 2.6 (S.D.) Torr (p less than 0.05) and plasma bicarbonate decreased by 2.9 +/- 1.1 mM (p less than 0.01). During CMA administration, the atmospheric hypoxic ventilatory response (HVR), assessed by minute ventilatory (delta VI/delta SaO2), and occlusion pressure responses (delta P .2/delta SaO2), significantly increased about 1.9 (p less than 0.05) and 1.6 times (p less than 0.01) compared to the placebo response, respectively. The calculated normocapnic HVR (delta VI/delta SaO2) increased about 2.3 times the placebo run. Hypoxic response evaluated by the withdrawal test, which represents the peripheral chemosensitivity without involving the influence due to secondary hypoxic depression, was about 1.7 times the placebo response (p less than 0.05). We conclude that CMA augments hypoxic respiratory chemosensitivity.