Head-down tilt (HDT) bed rest was used in this study to achieve physiological manipulation of the plasma concentrations of atrial natriuretic peptide (ANP) and the hormones of the renin-angiotensin system. The purpose of this was to achieve a parallel with previous animal experiments in which blockade of the renin-angiotensin system caused significant increases in low-frequency spectral power of heart rate variability, presumably as a consequence of increased blood pressure variability, although this was not measured in these animal experiments. Eight healthy young men completed 10 h of seated control and 6 degrees HDT. To gain a more complete understanding of the interactions between hormonal and neural factors involved in cardiovascular regulation, we measured heart rate, systolic and diastolic pressure variabilities, plasma hormone concentrations, and blood flow to selected vascular beds by pulsed Doppler. Resting R-R interval was not significantly different between seated and HDT tests. Stroke volume and cardiac output were elevated in the first 1-2 h of HDT (P < 0.05), whereas each of systolic (P < 0.01) and diastolic (P < 0.0001) pressures was lower during HDT. Plasma ANP increased as much as 70% during HDT (P < 0.0001). Total variability in each of R-R interval and diastolic blood pressure was reduced during HDT (P < 0.001). Thus, at a time when plasma renin activity was decreased as much as 40% (P < 0.0001), there was in fact a decrease in the variability of R-R interval and diastolic blood pressure in contrast to the hypothesized increase such as found in previous animal experimentation. The data were compatible with tighter autonomic regulation of heart rate about the ideal mean value during HDT.