Skeletal muscles are important reflexogenic areas of the cardiovascular system. The afferent pathways of the reflex loops involve slow-conducting group III and group IV fibers that are excited by mechanical and chemical events in the muscle. The present paper reviews a series of experiments dealing with the question of whether those afferents are also influenced by gravitational forces. The results of these studies suggest the following answers: 1) gravitational forces can modulate cardiovascular reflexes from exercising skeletal muscles. 2) This effect is primarily due to changes in the interstitial fluid volume rather than to a direct mechanical influence, venous pressure, or venous volume. 3) The amplitudes of heart rate and blood pressure responses during exercise are inversely related to the local interstitial volume. Measurements during postexercise circulatory arrest indicate that this sensitivity is mainly mediated by muscle chemoreceptors. These receptors, which also contribute to the spinal control of movement, generally appear to be sensitized by regional fluid losses and desensitized by overhydration of their environment.