Introduction: Deep brain stimulation applied to the dorsal periaqueductal grey matter (PAG) in humans has been shown to increase arterial blood pressure during rest and resist postural blood pressure fall on standing whereas stimulation in the ventral PAG decreases BP during rest. The mechanism by which this effect is mediated is not clear. The low frequency (LF) component of heart rate variability (HRV) is generally accepted to represent sympathetic nervous system activity. The aim of this experiment was to measure cardiovascular responses during PAG stimulation and correlate them to changes in sympathetic nervous system activity. Methods: Five consecutive male patients of a mean age of 49.1 years underwent PAG stimulation for intractable pain syndromes. Intra-operative, continuous heart rate and invasive blood pressure recordings were made in patients who were awake (4 patients) or under general anaesthesia (1 patient). Recordings were made for 100 seconds before stimulation, 100 seconds during stimulation at one or two electrode locations within the PAG and for 100 seconds after stimulation. This yielded recordings from a total of 7 PAG electrode positions across patients. Results: PAG stimulation altered systolic blood pressure (SBP), diastolic blood pressure and heart rate. During stimulation SBP increased in 3 cases by 7.2-10.2mmHg, decreased in 2 cases by 3.1-11.5mmHg and was unchanged in 2 cases. HRV also changed during stimulation. LF power increased when SBP increased and decreased when SBP decreased. Furthermore changes in SBP during stimulation correlated positively with changes in LF power (Pearson’s r=0.82, p=0.024, n=7). Conclusions: PAG stimulation produced positively-correlated changes in SBP and LF power. This therefore suggests that PAG stimulation alters cardiovascular performance via modulation of sympathetic nervous system activity.