We measured the isocapnic hypoxic ventilatory response and the hypercapnic ventilatory response by using rebreathing techniques in five normal subjects (ages 37-47 yr) before, during, and after 16 days of exposure to microgravity (microG). Control measurements were performed with the subjects in the standing and supine postures. In both microG and in the supine position, the hypoxic ventilatory response, as measured from the slope of ventilation against arterial O(2) saturation, was greatly reduced, being only 46 +/- 10% (microG) and 52 +/- 11% (supine) of that measured standing (P < 0.01). During the hypercapnic ventilatory response test, the ventilation at a PCO(2) of 60 Torr was not significantly different in microG (101 +/- 5%) and the supine position (89 +/- 3%) from that measured standing. Inspiratory occlusion pressures agreed with these results. The findings can be explained by inhibition of the hypoxic but not hypercapnic drive, possibly as a result of an increase in blood pressure in carotid baroreceptors in microG and the supine position.