The objective of the present study was to evaluate the influence of posture on the responses of blood pressure (BP) and heart rate (HR) to the Valsalva manoeuvre (VM). Neurohumoral activation, as well as changes in intravascular and intracardiac volumes and pressures, are well known effects of orthostatic stress. These changes are likely to have significant effects on cardiovascular reflexes, such as the response to the VM. However, the influence of posture on the VM has not been intensively evaluated, except for a few studies involving small sex- and age-selected case series. We therefore investigated the effects of posture on the VM in a larger non-selected group of healthy control subjects. In 19 healthy volunteers (ten female/nine male; age range 20-72 years, mean age 43 years), two reproducible VMs (40 mmHg; 15 s) were performed after 10 min of supine rest, 10 min of sitting and 10 min of standing. HR and BP were monitored continuously. End-diastolic volume, total peripheral resistance and cardiac output were calculated at baseline for each position. We found that assuming an upright position resulted in increases in total peripheral resistance and HR, accompanied by decreases in end-diastolic volume and cardiac output. The fall in BP during early phase II and the BP overshoot during phase IV were clearly more pronounced with increasing orthostatic stress, whereas the rise in BP during late phase II remained unchanged; pulse pressure was more compressed during phase II, but higher during phase IV. The Valsalva ratio was not significantly affected, but baroreflex gain (calculated from early phase II) was significantly decreased in the upright position. While a reduced late phase II was observed on one occasion in each of the lying and sitting positions, three abnormal responses were observed during standing. We conclude that posture has a significant influence on BP responses to the VM, probably resulting from changes in the intrathoracic blood volume. Standing results in a lower rate of 'flat-top' responses, but also seems to reduce the specificity of this test. Sympathetic activation in the upright position seems to blunt baroreflexes, leading to similar HR responses in spite of larger changes in BP.