We studied cardiovascular responses to lower-body negative pressure (LBNP) following 1 hour (h) of 6 degrees head-down tilt to determine whether a redistribution of blood volume toward the central circulation modifies the subsequent response to orthostatic stress. Responses of 12 men, ages 30-39 years, were evaluated by electrocardiography, impedance cardiography, sphygmomanometry, and measurement of calf circumference. During the LBNP that followed head-down tilt--as compared with control LBNP (no preceding head-down tilt)--subjects had smaller stroke volume and cardiac output, greater total peripheral resistance, and less calf enlargement. These differences reflect differences in the variables immediately preceding LBNP. Magnitudes of the responses from pre-LBNP to each pressure stage of the LBNP procedure did not differ between protocols. Mean and diastolic arterial pressures were slightly elevated after LBNP-control, but they fell slightly during LBNP post-tilt. These cardiovascular responses to simulated gravitational stress following head-down tilt may reflect the manner in which adaptation to microgravity affects subsequent responses to orthostatic stress on return to Earth.