Stretch-sensitive muscle mechanoreceptive afferents are known to decrease resting vagal tone and increase heart rate (HR) (Gladwell et al., 2005). This HR rise can be seen even when opposed by baroreflex activation, induced by neck pressure change, in resting subjects. Sustained isometric exercise and subsequent post- exercise circulatory occlusion (PECO) causes an exercise pressor reflex and hence increases baroreceptor activation. We have shown previously that during baroreflex activation by PECO, passive stretch of the human calf muscle does increase HR by a similar magnitude to that seen at rest (Drew et al., 2006). However, it remains unclear whether this effect is dependent upon metabolite sensitisation of the mechanoreceptive afferents as a constant inhibitory mechanoreflex input from the muscle acting against an increased excitatory input from the baroreflex would not be expected to result in the same HR rise. By activating muscle mechanoreceptive afferents during PECO in either the limb that generated the exercise pressor reflex or the contralateral previously inactive limb, a sensitising effect of trapped metabolites on the reflex could be revealed. With local ethical committee approval, subjects rested for 5mins and then on separate occasions performed each of the following trials. They either rested for a further 1.5mins with occlusion of the circulation to the right leg (R-CON) or left leg (L-CON), or performed 1.5mins of one-legged isometric plantarflexor exercise at 50% of their maximal voluntary contraction with either the right calf (R-EX) or left calf (L-EX). This activated the muscle metaboreflex and increased mean arterial pressure (MAP) by 8±1 and 6±1 mmHg for the right and left legs, respectively, during 3.5 min of PECO. This was followed by a further 3mins of concurrent occlusion and sustained passive stretch of the right calf muscle in all trials. During PECO in the R-EX trial (metaboreflex activation in the right calf), concurrent passive stretch of the right calf increased HR by a similar magnitude compared to during the R-CON trial (3±2 v 4±2 b.min-1, respectively). However, in the L-EX trial (metaboreflex activation in the left calf), concurrent passive stretch of the right calf caused a smaller HR increase compared to both the R-EX (1±1 v 3±2 b.min-1, respectively), and L-CON (1±1 v 2±2 b.min-1, respectively) trials. This data suggests that trapped metabolites sensitise the muscle mechanoreceptive afferents, and is compatible with the idea that this facilitates their response to standardised mechanoreflex activation. This increased inhibitory reflex input is then more effectively able to oppose baroreflex-mediated excitation of cardiac vagal neurones.