The purpose of these experiments was to examine ventilatory and gas exchange responses to acute head-down tilt. Subjects (N = 5) participated in two series of head-down tilt experiments. Both experimental protocols involved movement from a near-vertical position (120 degrees) to a -30 degrees head-down position. One set of experiments employed venous occlusion (VO) in the legs during the first 30 s of tilt, while the second set was performed without occlusion (control experiment). Oxygen uptake (VO2), carbon dioxide output (VCO2) and expired ventilation (VE) increased significantly (p less than 0.05) above vertical values in both experimental conditions during the first 75 s following tilt. Further, VO2, VCO2, and VE were greater (p less than 0.05) during the VO experiment compared to control immediately following removal of venous occlusion. Although end-tidal CO2 tension (PETCO2) tended to increase following tilt, mean PETCO2 averaged over 15-s periods remained unaltered (p greater than 0.05) during tilt in both experimental protocols compared to the vertical position. These data demonstrate that acute head-down tilt results in an increase in VE and the general maintenance of isocapnia.