We have previously shown that activation of muscle receptors by passive stretch (PS) increases heart rate (HR) with little change in blood pressure (BP). We proposed that PS selectively inhibits cardiac vagal activity. We attempted to test this by performing PS during experimental alterations in vagal tone. Large decreases in vagal tone were induced using either glycopyrrolate or mild rhythmic exercise. Milder alterations in vagal tone were achieved by altering carotid baroreceptor input: neck pressure (NP) or neck suction (NS). PS of the triceps surae was tested in 14 healthy human volunteers. BP, ECG and respiration were recorded. PS alone caused a significant decrease (P <0.05) in R-R interval (962 +/- 76 ms at baseline compared to 846 +/- 151 ms with PS), and showed a reduction in HR variability, which was not significant. The decrease in R-R interval with PS was significantly less (P <0.05, n = 3) following administration of glycopyrrolate (-8.1 +/- 4.5 ms) compared to PS alone (-54 +/- 11 ms), and also with PS during handgrip, (+10 +/- 10 ms) compared with PS alone (-74 +/- 15 ms) (P <0.05, n = 5). Milder reductions in vagal activity (NP) resulted in a small but insignificant further decrease in R-R interval in response to PS (-107 +/- 17 ms compared to PS alone -96 +/- 13 ms, n = 5). Mild increases in vagal activity (NS) during PS resulted in smaller decreases in R-R interval (-39 +/- 5.5 ms) compared to PS alone (-86 +/- 17 ms) (P <0.05, n = 8). BP was not significantly changed by stretch in any tests. The results indicate that amongst muscle receptors there is a specific group activated by stretch that selectively inhibit cardiac vagal tone to produce tachycardia.