Orthostatic intolerance is a predictable but poorly understood consequence of space travel. Because arterial baroreceptors modulate abrupt pressure transients, we tested the hypothesis that spaceflight impairs baroreflex mechanisms. We studied vagally mediated carotid baroreceptor-cardiac reflex responses (provoked by neck pressure changes) in the supine position and heart rate and blood pressure in the supine and standing positions in 16 astronauts before and after 4- to 5-day Space Shuttle missions. On landing day, resting R-R intervals and standard deviations, and the slope, range, and position of operational points on the carotid transmural pressure-sinus node response relation were all reduced relative to preflight. Stand tests on landing day revealed two separate groups (one maintained standing arterial pressure better) that were separated by preflight slopes, operational points, and supine and standing R-R intervals and by preflight-to-postflight changes in standing pressures, body weights, and operational points. Our results suggest that short-duration spaceflight leads to significant reductions in vagal control of the sinus node that may contribute to, but do not account completely for, orthostatic intolerance.