We have previously shown that activation of muscle receptors by passive stretch (PS) increases heart rate (HR) with little change in blood pressure (BP) (Gladwell and Coote, 2002). We propose that the muscle mechanoreceptors inhibit cardiac vagal activity and therefore alter the baroreceptor-HR reflex. In this set of studies we attempted to test this by performing PS during alterations in vagal tone. A large decrease in vagal tone was caused both pharmacologically and by using mild rhythmic exercise. Further, milder alterations in vagal tone were achieved by altering carotid baroreceptor input: using neck pressure (NP) and neck suction (NS) to cause a small decrease and increase, respectively. Following local health authority ethical approval, fourteen (mean± SD, 21.9±2 years) healthy human volunteers participated in four different studies. In all experiments subjects lay supine allowing PS of the triceps surae. BP (FINAPRES), ECG, and respiration were recorded. Paired t-tests were performed between the 2 conditions within each study (P≤ 0.05). PS alone caused a significant decrease (P≤ 0.05) in RR interval 962±76ms at baseline compared to 846±151ms with PS, with a reduction in heart rate variability but without a significant change in BP. In study 1, (n=3), glycopyrrolate was infused i.v. (5μg/kg/h) following a bolus dose of 300 μg/kg. In study 2, (n=5) PS was performed with and without rhythmical handgrip (10% MVC). The decrease in RR interval with PS was significantly decreased by reducing vagal output using glycopyrrolate during PS (−8.1±4.5ms) compared to PS alone (−54±11ms) and by applying PS during handgrip (10±10ms) compared to PS alone (−74±15ms; P≤0.05). In study 3 and 4 (n=8), PS was applied with NP and NS. Interestingly, reducing baroreceptor input with NP resulted in a small but insignificant further decrease in R-R interval in response to PS (−107±17ms) compared to PS alone (−96±13 ms; P>0.05). Conversely, increasing baroreceptor input with NS during PS there was a significantly smaller decrease in R-R interval (−39±5.5 ms) compared to PS alone (−86±17ms) (P≤0.05). BP was not significantly different in any of the four studies (P>0.05). These data support the idea that muscle mechanoreceptors alter the excitation of cardiac vagal neurones. Further, it is likely that in this experimental model the carotid baroreceptors and the muscle mechanoreceptors interact at the level of the cardiac vagal neurones rather than earlier in the baroreceptor pathway at the nucleus tractus solitarii.