This investigation was conducted to test the following hypotheses: 1) If simulated orthostasis (LBNP) reduces plasma cGMP; 2) if simulated microgravity alters any such LBNP-induced effect; and 3) if simulated microgravity reduces resting plasma cGMP levels. In addition, we studied the time-course of thoracic impedance during, LBNP and asked if there is heart rate/blood pressure reduction after LBNP. During real and simulated spaceflight, blood is re-distributed throughout the vasculature along the body axis, vascular mechanoreceptor loads are altered, "excess" fluid is lost from the organism, and reflexly connected endocrine systems adapt with accompanying changes of hormone output. Altered steady-state plasma concentrations of volume sensitive hormones have been observed inflight as well as postflight. Hormones play a salient role in volume regulation but have barely been studied during microgravitational conditions in conjunction with lower body suction (LBNP). We used LBNP as an analogue to orthostatic stress since this model is useful to investigate, on quantitative grounds, hormone concentration changes as a function of cardiovascular stress in simulated weightless conditions. Earlier we reported consistently reduced plasma ANP and cGMP levels in a case study (14 mo spaceflight); transient hormonal changes after LBNP (as % of pre-LBNP values) were not different (p>0.05) from ground-control findings, and other hormone levels did not consistently deviate from ground control values. This is important since transmural central venous pressure which influences ANP output from the heart, and is elevated despite decreased CVP in parabolic flight, might be downregulated on a long-term basis. TCVP has not yet been measured inflight.