A decrease in orthostatic tolerance following exposure to microgravity or head down bed rest (HDBR) is frequently observed and is thought to be multifactorial in origin. Recently published observations by Buckey et al. indicate that the inability to regulate peripheral vascular resistance during an orthostatic stress after spaceflight could be another important mechanism for orthostatic intolerance. Previous investigations have revealed that a local veno-arteriolar reflex is present in cutaneous, subcutaneous and muscle tissue. The reflex response is elicited in response to an increase in transmural venular pressure of about 25 mmHg or more. The local veno-arteriolar reflex acts in concert with centrally elicited sympathetic activity to regulate vascular resistance. During standing, the local veno-arteriolar reflex participates as a mechanism to increase peripheral vascular resistance independently of sympathetically mediated vasoconstrictor responses. During HDBR the local veno-arteriolar reflex is inactive for a prolonged period of time. Therefore we hypothesized that the veno-arteriolar reflex in the skin is attenuated immediately after prolonged HDBR and that an attenuation of the response may contribute to post-HDBR orthostatic intolerance.